Is BRCA2 p.Val3091Asp (c.9272T>A) pathogenic?

BRCA2 p.Val3091Asp (c.9272T>A) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-20). AlphaMissense: likely pathogenic (0.9628); Absent from gnomAD v4.1; Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Val3091Asp (c.9272T>A)?

BRCA2 p.Val3091Asp (c.9272T>A) is associated with BRCA2-related cancer predisposition (ClinVar).

How common is BRCA2 p.Val3091Asp (c.9272T>A) in the general population?

BRCA2 p.Val3091Asp (c.9272T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Val3091Asp (c.9272T>A)?

AlphaMissense predicts likely pathogenic (score 0.9628) — an in-silico prediction, not a clinical call.

BRCA2 p.Val3091Asp

c.9272T>A · VCV3778945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9628 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.9628	likely pathogenic · top 1% in BRCA2
REVEL	0.779	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Val3091Asp
Coding: c.9272T>A
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32394704 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Disease context

BRCA2-related cancer predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Val3091Ile Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Val3091= Likely benign ★★ same residue
BRCA2 c.517-2A>G Pathogenic ★★★ same condition
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.631+4A>G Likely pathogenic ★★★ same condition
BRCA2 c.632-3C>G Likely pathogenic ★★★ same condition
BRCA2 c.6938-2A>G Pathogenic ★★★ same condition
BRCA2 c.7805+3A>C Likely 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-val3091asp (accessed [today's date]).

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