Is BRCA2 p.Ala3351Pro (c.10051G>C) pathogenic?

BRCA2 p.Ala3351Pro (c.10051G>C) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-22). AlphaMissense: ambiguous (0.4382); Absent from gnomAD v4.1; Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 p.Ala3351Pro (c.10051G>C)?

BRCA2 p.Ala3351Pro (c.10051G>C) is associated with Breast and/or ovarian cancer (ClinVar).

How common is BRCA2 p.Ala3351Pro (c.10051G>C) in the general population?

BRCA2 p.Ala3351Pro (c.10051G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Ala3351Pro (c.10051G>C)?

AlphaMissense predicts ambiguous (score 0.4382) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala3351Pro

c.10051G>C · rs786204285 · VCV188442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4382 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.4382	ambiguous · top 10% in BRCA2
REVEL	0.235	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Pangolin	Δ0.26	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.5	GERP -0.76, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	24.7	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.Ala3351Pro
Coding: c.10051G>C
MANE Select: NM_000059
dbSNP: rs786204285
Type: single nucleotide variant
Location: chr13:32398564 (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

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Ala3351= Likely benign ★★★ same residue
BRCA2 p.Ala3351Ser Uncertain significance ★ ⚠ same residue
BRCA2 p.Asp2723Val Pathogenic/Likely pathogenic ★★ same condition
BRCA2 p.Leu2653Pro Pathogenic/Likely pathogenic ★★ same condition
BRCA2 p.Pro3300Ser Uncertain significance ★★ same condition
BRCA2 c.316+12A>G Benign/Likely benign ★★ same condition
BRCA2 c.516+14C>T Benign/Likely benign ★★ same condition
BRCA2 c.632-69T>C Benign/Likely benign ★★ 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-ala3351pro (accessed [today's date]).

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