100+ Free ABPath Molecular Genetic Pathology Practice Questions

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Question 1

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Which of the following base pairs is held together by three hydrogen bonds in canonical Watson-Crick double-stranded DNA?

Adenine-Thymine

Adenine-Uracil

Guanine-Cytosine

Adenine-Guanine

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2026 Statistics

Key Facts: ABPath Molecular Genetic Pathology Exam

~200

Multiple-Choice Questions

Joint ABPath/ABMGG MGP exam

~4 hours

Total Exam Duration

One-day computer-based, Pearson VUE

$2,100

ABPath Exam Fee (2026)

Includes $200 non-refundable administrative fee

20%

Molecular Techniques Weight

Largest single content domain on MGP outline

2 boards

Joint Certification

ABPath + ABMGG share identical exam

12 months

ACGME MGP Fellowship

Required after primary AP/CP certification

The ABPath Molecular Genetic Pathology subspecialty exam is a one-day computer-based exam of approximately 200 single-best-answer questions over ~4 hours, jointly administered with the American Board of Medical Genetics and Genomics (ABMGG). 2026 ABPath subspecialty fee: $2,100 (includes $200 non-refundable administrative fee). Eligibility requires ABPath primary certification (AP, CP, or AP/CP), completion of an ACGME-accredited 12-month Molecular Genetic Pathology fellowship, and an active unrestricted medical license. Pathologist candidates apply through ABPath via the PATHway portal during the February 16 – May 15, 2026 application window; geneticist candidates apply through ABMGG. Content spans nucleic acid biochemistry, molecular techniques (PCR/Sanger/NGS/FISH/microarray), bioinformatics and ACMG/AMP variant interpretation, inherited disease, pharmacogenomics, hematologic malignancy diagnostics, solid tumor molecular profiling, HLA and identity testing, infectious disease molecular diagnostics, prenatal/PGT testing, and lab management/regulatory.

Sample ABPath Molecular Genetic Pathology Practice Questions

Try these sample questions to test your ABPath Molecular Genetic Pathology exam readiness. Each question includes a detailed explanation. Start the interactive quiz above for the full 100+ question experience with AI tutoring.

1Which of the following base pairs is held together by three hydrogen bonds in canonical Watson-Crick double-stranded DNA?

A.Adenine-Thymine

B.Adenine-Uracil

C.Guanine-Cytosine

D.Adenine-Guanine

Explanation: G-C base pairs form three hydrogen bonds, while A-T pairs form only two. This is why GC-rich regions of the genome have higher melting temperatures (Tm), an essential consideration when designing PCR primers or interpreting denaturation profiles in HRM analysis.

2What is the approximate size of the human haploid nuclear genome?

A.30 megabases

B.300 megabases

C.3 gigabases

D.30 gigabases

Explanation: The human haploid nuclear genome contains approximately 3 billion base pairs (3 Gb) distributed across 22 autosomes plus an X or Y. The mitochondrial genome adds an additional 16,569 bp, present in many copies per cell.

3A pathology resident asks why mitochondrial DNA testing for MELAS (m.3243A>G) requires evaluation of multiple tissue types. Which property of mitochondrial DNA best explains this?

A.Mitochondrial DNA undergoes Mendelian inheritance

B.Heteroplasmy levels vary between tissues and over time

C.Mitochondrial DNA is identical to nuclear DNA

D.Mitochondrial DNA is not subject to mutation

Explanation: Heteroplasmy — the coexistence of mutant and wild-type mtDNA in a single cell — varies markedly across tissues due to mitotic segregation. Blood may have low heteroplasmy while urinary epithelium or muscle has clinically relevant levels, which is why urine sediment or muscle biopsy is preferred for MELAS testing.

4A 4-year-old with severe hypotonia, hyperphagia, and obesity is suspected to have Prader-Willi syndrome. Which mechanism most commonly causes Prader-Willi syndrome?

A.Maternal deletion of 15q11-q13

B.Paternal deletion of 15q11-q13

C.Maternal uniparental disomy of chromosome 15

D.Paternal uniparental disomy of chromosome 15

Explanation: Prader-Willi syndrome is caused by loss of the paternally expressed genes at 15q11-q13. About 70% of cases are due to paternal deletion; 25% are due to maternal uniparental disomy. Methylation-specific PCR or methylation-sensitive MLPA detects all three mechanisms (deletion, mUPD, imprinting center defect) in a single assay.

5Loss of which mismatch repair protein is most commonly associated with sporadic colorectal cancers exhibiting microsatellite instability?

A.MSH2

B.MSH6

C.MLH1 (via promoter hypermethylation)

D.PMS2

Explanation: About 15% of sporadic colorectal cancers show MSI, the vast majority due to MLH1 promoter hypermethylation, often associated with BRAF V600E. In contrast, Lynch syndrome MSI cancers are typically driven by germline mutations in MLH1, MSH2, MSH6, or PMS2 (or EPCAM deletions affecting MSH2).

6Which enzyme is most commonly used in standard PCR amplification because of its thermostability?

A.DNA polymerase I (Klenow fragment)

B.Taq polymerase

C.T7 RNA polymerase

D.Reverse transcriptase

Explanation: Taq polymerase, isolated from Thermus aquaticus, is heat-stable and survives the 95 degrees C denaturation step in each PCR cycle. Higher-fidelity proofreading enzymes such as Pfu or Phusion are preferred when sequence accuracy is critical (e.g., for cloning or Sanger template generation).

7In a quantitative real-time PCR assay using a standard curve, what does the cycle threshold (Ct) value represent?

A.The cycle at which fluorescence reaches a fixed background-subtracted threshold

B.The total number of PCR cycles performed

C.The melting temperature of the amplicon

D.The annealing temperature of the primers

Explanation: Ct is the cycle at which fluorescence crosses a defined threshold above background. Lower Ct values correspond to higher target concentrations. Each one-cycle Ct difference represents approximately a 2-fold change in template under ideal (100% efficient) amplification conditions.

8Sanger sequencing relies on the incorporation of which type of nucleotide to terminate chain elongation?

A.Dideoxyribonucleotides (ddNTPs)

B.Modified ribonucleotides

C.Locked nucleic acids (LNAs)

D.Phosphorothioate-modified nucleotides

Explanation: Sanger sequencing uses fluorescently labeled dideoxynucleotides (ddATP, ddCTP, ddGTP, ddTTP) that lack a 3'-OH, terminating elongation when incorporated. Capillary electrophoresis separates the labeled fragments by size, and the trailing peak in each base position is read as the consensus base.

9What is the typical analytical limit of detection for a heterozygous variant by traditional Sanger sequencing?

A.Approximately 1% variant allele fraction

B.Approximately 5% variant allele fraction

C.Approximately 15-20% variant allele fraction

D.Approximately 50% variant allele fraction

Explanation: Sanger sequencing reliably detects variants present at roughly 15-20% allele fraction or higher. Below that, the minor peak becomes indistinguishable from background. NGS or droplet digital PCR are preferred when low-level mosaicism, ctDNA, or minimal residual disease detection is required.

10Which step in a typical Illumina-based NGS workflow most directly enables clonal amplification of individual library molecules prior to sequencing-by-synthesis?

A.Adapter ligation to fragmented DNA

B.Bridge amplification on the flow cell

C.Capillary electrophoresis size selection

D.Reverse transcription of mRNA to cDNA

Explanation: After adapter ligation, library molecules hybridize to oligos on the flow cell and are clonally amplified through bridge amplification, generating millions of clusters. Each cluster yields the signal for one read during sequencing by synthesis with reversible-terminator dNTPs.

About the ABPath Molecular Genetic Pathology Exam

The ABPath Molecular Genetic Pathology (MGP) exam is a joint subspecialty certification co-sponsored by the American Board of Pathology (ABPath) and the American Board of Medical Genetics and Genomics (ABMGG). It validates expertise in clinical molecular diagnostics across germline disease, hematologic malignancies, solid tumor profiling, infectious disease, pharmacogenomics, identity/HLA testing, and laboratory management. Pathologist candidates apply through ABPath; geneticist candidates apply through ABMGG; the certification is equivalent. Eligibility requires primary ABPath certification (AP, CP, or AP/CP) plus completion of an ACGME-accredited Molecular Genetic Pathology fellowship (typically 12 months) and an active unrestricted medical license.

Questions

200 scored questions

Time Limit

~4 hours (one-day computer-based)

Passing Score

Criterion-referenced scaled standard set by the joint ABPath/ABMGG Molecular Genetic Pathology Test Committee (modified Angoff)

Exam Fee

$2,100 ABPath subspecialty certification fee (ABPath 2026) (ABPath (joint certification with American Board of Medical Genetics and Genomics / ABMGG))

ABPath Molecular Genetic Pathology Exam Content Outline

Nucleic Acid Biochemistry, Genome Organization & Inheritance

DNA/RNA structure, base pairing, replication, transcription, translation, mitochondrial DNA biology and heteroplasmy, imprinting (Prader-Willi, Angelman, Beckwith-Wiedemann), DNA repair (mismatch repair, base excision repair), modes of inheritance, anticipation, and X-inactivation.

18%

Molecular Techniques

Conventional and quantitative PCR, primer/probe design, Sanger sequencing and chain termination, capillary electrophoresis fragment analysis, FISH (break-apart, dual-fusion, locus-specific), chromosomal microarray (aCGH and SNP arrays), MLPA, methylation analysis (bisulfite, MSP, MS-MLPA), droplet digital PCR, NGS chemistries (Illumina, Ion Torrent, ONT, PacBio), library preparation, hybrid capture vs amplicon, and UMIs.

13%

Bioinformatics & Variant Interpretation

Reference genomes (GRCh37/GRCh38/T2T), alignment (BWA), variant callers (GATK), HGVS nomenclature, ACMG/AMP germline guidelines (PVS1-BP7), AMP/ASCO/CAP somatic variant tiers (I-IV), population databases (gnomAD), ClinVar, COSMIC, splicing prediction, in silico tools (REVEL, CADD, SpliceAI), TMB, MSI, and ACMG SF v3.2 secondary findings.

10%

Inherited Disease Genetics

Cystic fibrosis (CFTR), fragile X (FMR1), Huntington (HTT), spinal muscular atrophy (SMN1/SMN2), Duchenne/Becker (DMD), hereditary hemochromatosis (HFE), Lynch syndrome (MLH1/MSH2/MSH6/PMS2/EPCAM), hereditary breast/ovarian (BRCA1/2/PALB2), thalassemias and hemoglobinopathies, mitochondrial disorders (MELAS, MERRF, LHON), and trinucleotide repeat disorders.

Pharmacogenomics

CYP2C19/clopidogrel, TPMT/NUDT15 thiopurines, DPYD fluoropyrimidines, HLA-B*15:02 carbamazepine, HLA-B*57:01 abacavir, VKORC1/CYP2C9 warfarin, UGT1A1 irinotecan, G6PD oxidant drugs, CYP2D6 codeine/tamoxifen, CPIC and PharmGKB clinical guidelines, and FDA pharmacogenomic biomarkers in drug labeling.

10%

Hematologic Malignancy Molecular Diagnostics

BCR-ABL1 in CML/ALL, IS-standardized monitoring (MMR, MR4, MR4.5), AML markers (NPM1, FLT3-ITD/TKD, CEBPA, RUNX1, IDH1/2, TP53, ASXL1), APL t(15;17) PML-RARA, MPN driver mutations (JAK2 V617F, CALR, MPL), CLL prognostic markers (TP53/del17p, IGHV, NOTCH1), lymphoma cytogenetics (MCL t(11;14), FL t(14;18), Burkitt MYC), HCL BRAF V600E, myeloma FISH high-risk panel, and MRD assays.

10%

Solid Tumor Molecular Profiling

NSCLC EGFR/ALK/ROS1/BRAF/KRAS G12C/MET ex14/RET/NTRK, colorectal extended RAS/BRAF/HER2/MMR, melanoma BRAF/NRAS/KIT, breast ER/PR/HER2/ESR1/PIK3CA/AKT1/PTEN, GIST KIT/PDGFRA, thyroid BRAF/RET, sarcoma fusions (EWSR1, SS18-SSX, FUS-DDIT3, COL1A1-PDGFB), liquid biopsy/ctDNA, NTRK and RET tissue-agnostic indications, and MSI/TMB for immunotherapy.

HLA Typing & Transplantation Diagnostics

HLA nomenclature (alleles, fields, ambiguities), high-resolution typing methods (NGS, SBT, SSO, SSP), HSCT donor matching (10/10, 12/12), solid organ virtual crossmatch, Luminex single-antigen bead, chimerism testing by STR after allogeneic transplant, HLA-disease associations (HLA-B27, HLA-DR3/DR4, narcolepsy, celiac), and HLA pharmacogenomics (B*57:01, B*15:02, B*58:01).

Infectious Disease Molecular Diagnostics

HIV-1 RNA viral load and resistance genotyping (Stanford HIVdb), HCV RNA quantification and SVR12, HBV viral load (WHO IU/mL), HPV primary screening with HPV 16/18 genotyping, CMV/EBV/BKV in transplant (WHO standards), HSV PCR for encephalitis/meningitis, MTB GeneXpert with rpoB rifampin resistance, Clostridioides difficile, multiplex respiratory panels, Lyme PCR, and SARS-CoV-2 RT-PCR/sequencing for variant surveillance.

Prenatal & Preimplantation Testing

Maternal serum screening, cell-free DNA NIPT (sensitivity, specificity, fetal fraction, no-call management, confined placental mosaicism), CVS and amniocentesis, prenatal CMA as first-tier for structural anomalies, expanded carrier screening (ACOG/ACMG Tier 3), preimplantation genetic testing (PGT-A, PGT-M, PGT-SR), and trophectoderm biopsy/amplification artifacts.

Identity Testing

STR loci (CODIS), parentage/relationship testing, engraftment chimerism, sample mix-up detection in clinical specimens, ancestry-informative markers, and forensic principles relevant to molecular pathology laboratories.

Lab Management, Quality Assurance & Regulation

CLIA high-complexity requirements, CAP Molecular Pathology (MOL) checklist, LDT validation (accuracy, precision, LoD, LoQ, reportable range, reference range), bioinformatics pipeline validation per AMP/CAP, GIAB reference samples (NA12878/HG002), proficiency testing and alternative assessments, FDA 2024 LDT final rule, GINA, HIPAA genetic privacy, CPT molecular Tier 1/Tier 2/GSP coding, FFPE preanalytics and formalin artifacts, RNA integrity, and reporting per AMP/ASCO/CAP.

How to Pass the ABPath Molecular Genetic Pathology Exam

What You Need to Know

Passing score: Criterion-referenced scaled standard set by the joint ABPath/ABMGG Molecular Genetic Pathology Test Committee (modified Angoff)
Exam length: 200 questions
Time limit: ~4 hours (one-day computer-based)
Exam fee: $2,100 ABPath subspecialty certification fee (ABPath 2026)

Keys to Passing

Complete 500+ practice questions
Score 80%+ consistently before scheduling
Focus on highest-weighted sections
Use our AI tutor for tough concepts

ABPath Molecular Genetic Pathology Study Tips from Top Performers

1Master molecular techniques deeply — Sanger LoD ~15-20%, NGS targeting 500x for somatic 5% VAF, ddPCR Poisson statistics for <0.1% rare variants, and ASCO/CAP HER2 ISH algorithm cutoffs (ratio ≥2.0 with copy ≥4.0)

2Memorize ACMG/AMP germline rules (PVS1, PS1-PS4, PM1-PM6, PP1-PP5, BA1, BS1-BS4, BP1-BP7) and AMP/ASCO/CAP somatic tiers (Tier I = strong clinical significance/FDA-approved, Tier II = potential, Tier III = unknown, Tier IV = benign)

3Know the BCR-ABL1 International Scale cold: MMR ≤0.1%, MR4 ≤0.01%, MR4.5 ≤0.0032%, and which thresholds qualify for treatment-free remission attempts

4Learn pharmacogenomic priority pairs from CPIC: CYP2C19/clopidogrel (PM → alternative), TPMT-NUDT15/thiopurines, DPYD/5-FU, HLA-B*57:01/abacavir, HLA-B*15:02/carbamazepine in Asian ancestry, VKORC1+CYP2C9/warfarin, UGT1A1*28/irinotecan

5For lab management: know CLIA validation requirements (accuracy, precision, LoD, analytical specificity, reportable range, reference range), CAP MOL checklist, GIAB reference samples (NA12878/HG002 for benchmarking), and the FDA 2024 LDT final rule's 5-stage 4-year phase-out

Frequently Asked Questions

What is the ABPath Molecular Genetic Pathology (MGP) subspecialty exam?

The ABPath Molecular Genetic Pathology exam is a joint subspecialty certification co-sponsored by the American Board of Pathology (ABPath) and the American Board of Medical Genetics and Genomics (ABMGG). It validates expertise in molecular diagnostics across germline disease, hematologic malignancies, solid tumor profiling, infectious disease, pharmacogenomics, HLA/identity testing, and clinical laboratory management. Pathologist candidates apply through ABPath; geneticist candidates apply through ABMGG. The resulting certificate is equivalent.

How many questions are on the ABPath MGP exam and how long is it?

The exam is a one-day computer-based examination of approximately 200 single-best-answer multiple-choice questions over roughly 4 hours of testing time, administered at Pearson VUE Professional Test Centers. Unlike the AP primary exam, there is no virtual microscopy section. Score reports provide pass/fail plus diagnostic performance by content domain.

What is the passing score for the ABPath MGP exam?

The exam uses a criterion-referenced scaled passing standard set by the joint ABPath/ABMGG Molecular Genetic Pathology Test Committee through a modified Angoff process. Candidates are measured against a fixed content-expert standard rather than curved against peers. The committee periodically reviews and re-sets the passing standard as content and clinical practice evolve.

What are the eligibility requirements for the ABPath MGP exam?

Pathologist candidates must (1) hold primary ABPath certification in AP, CP, or AP/CP; (2) complete an ACGME-accredited Molecular Genetic Pathology fellowship (typically 12 months); and (3) maintain an active unrestricted medical or osteopathic license. Simultaneous training with another ACGME pathology subspecialty fellowship is allowed with prior ABPath approval (Pathway A or B). Geneticists apply through ABMGG with ABMGG-specific eligibility criteria.

How much does the ABPath MGP exam cost in 2026?

The 2026 ABPath subspecialty certification fee is $2,100, which includes a non-refundable $200 administrative fee. The application window is February 16 – May 15, 2026, with the exam administered September 8 – September 28, 2026 at Pearson VUE Professional Testing Centers. Geneticist candidates registering through ABMGG pay the fee set by ABMGG, which differs.

What are the highest-yield topics on the ABPath MGP exam?

Molecular techniques (~20%) is the largest single domain — master PCR/qPCR, Sanger limit-of-detection (~15-20%), NGS workflows (library prep, coverage targets, UMIs), FISH (break-apart for ALK, dual-probe HER2), MLPA for exon-level CNVs, and methylation analysis. Bioinformatics and variant interpretation (~15%) requires ACMG/AMP germline rules (PVS1-BP7) and AMP/ASCO/CAP somatic tiers (I-IV). Hematologic and solid-tumor diagnostics together account for ~24% — know BCR-ABL1 IS monitoring (MMR = ≤0.1%), MPN drivers (JAK2/CALR/MPL), NSCLC EGFR/ALK/KRAS G12C, colorectal extended RAS/BRAF/MMR, melanoma BRAF V600E, and GIST KIT/PDGFRA D842V. Inherited disease (~12%), pharmacogenomics (~8%), HLA (~5%), infectious disease (~8%), prenatal/PGT (~5%), and lab management (~10%) round out the blueprint.

How should I study for the ABPath MGP exam?

Use a 6-12 month structured plan during or after your Molecular Genetic Pathology fellowship. Build a foundation in molecular techniques (PCR/Sanger/NGS/FISH/microarray) and bioinformatics (ACMG/AMP, AMP/ASCO/CAP, gnomAD, ClinVar). Layer on disease-specific content: hematologic malignancies (BCR-ABL, FLT3, JAK2, CALR, MPL, MCL, FL, CLL), solid tumors (NSCLC, CRC, melanoma, breast, GIST, sarcoma fusions), pharmacogenomics (CPIC top-tier guidelines), infectious disease (HCV/HIV/HPV/CMV/MTB), prenatal (NIPT, PGT, expanded carrier), HLA/identity (chimerism, transplant), and lab management (CLIA, CAP MOL, validation, FDA LDT rule, GINA). Review Coleman's Molecular Pathology, AMP guidelines, ABPath Content Specifications, and complete thousands of practice questions. Take at least two timed full-length practice exams.

Is the ABPath MGP exam multi-board?

Yes. Molecular Genetic Pathology is a joint and equal certification of ABPath and the American Board of Medical Genetics and Genomics (ABMGG). Both boards share the same exam content, test committee, and passing standard. Candidates apply through their primary board: ABPath candidates through the ABPath PATHway portal; ABMGG candidates (typically clinical geneticists) through ABMGG. The resulting certificate is equivalent and recognized across both specialties.