Is BRCA2 p.Val3244Phe (c.9730G>T) pathogenic?

BRCA2 p.Val3244Phe (c.9730G>T) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-31). AlphaMissense: likely benign (0.083); Very rare (popmax 0.00446%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Val3244Phe (c.9730G>T)?

BRCA2 p.Val3244Phe (c.9730G>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Val3244Phe (c.9730G>T) in the general population?

BRCA2 p.Val3244Phe (c.9730G>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BRCA2 p.Val3244Phe (c.9730G>T)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

BRCA2 p.Val3244Phe

c.9730G>T · rs11571831 · VCV38263

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.327	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.48	GERP -4.7
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,000 alleles · very rare exomes 2/1,461,742 · genomes 0/152,258 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA2
Protein: p.Val3244Phe
Coding: c.9730G>T
MANE Select: NM_000059
dbSNP: rs11571831
Type: single nucleotide variant
Location: chr13:32398243 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3244: a UniProt-annotated variant site (in)

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 2

Similar variants

BRCA2 p.Val3244Ile Benign ★★★ same residue
BRCA2 p.Val3244Ala Uncertain significance ★★ ⚠ same residue
BRCA2 p.Val3244Leu Uncertain significance ★★ ⚠ same residue
BRCA2 p.Val3244= Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Val3244fs Pathogenic/Likely pathogenic ★★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca2-p-val3244phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown