Is BRCA2 p.Ala2951Pro (c.8851G>C) pathogenic?

BRCA2 p.Ala2951Pro (c.8851G>C) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.9671); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ala2951Pro (c.8851G>C)?

BRCA2 p.Ala2951Pro (c.8851G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ala2951Pro (c.8851G>C) in the general population?

BRCA2 p.Ala2951Pro (c.8851G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Ala2951Pro (c.8851G>C)?

AlphaMissense predicts likely pathogenic (score 0.9671) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala2951Pro

c.8851G>C · rs11571769 · VCV1764884

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9671	likely pathogenic · top 1% in BRCA2
REVEL	0.406	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	26.4	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

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.Ala2951Pro
Coding: c.8851G>C
MANE Select: NM_000059
dbSNP: rs11571769
Type: single nucleotide variant
Location: chr13:32379413 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2951: a UniProt-annotated variant site (in bc; benign; no effect on homology-directed repair activity)

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

Similar variants

BRCA2 p.Ala2951= Likely benign ★★★ same residue
BRCA2 p.Ala2951Thr Benign ★★★ same residue
BRCA2 p.Ala2951Gly Uncertain significance ★ ⚠ same residue
BRCA2 p.Ala2951Ser Likely benign ★ same residue
BRCA2 p.Ala2951fs 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-ala2951pro (accessed [today's date]).

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