Is BRCA2 p.Ala3029Val (c.9086C>T) pathogenic?

BRCA2 p.Ala3029Val (c.9086C>T) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.2331); Ultra-rare (popmax 0.0165%, mid); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 p.Ala3029Val (c.9086C>T)?

BRCA2 p.Ala3029Val (c.9086C>T) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Ala3029Val (c.9086C>T) in the general population?

BRCA2 p.Ala3029Val (c.9086C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BRCA2 p.Ala3029Val (c.9086C>T)?

AlphaMissense predicts likely benign (score 0.2331) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala3029Val

c.9086C>T · rs80359162 · VCV52744

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.2331 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.2331	likely benign
REVEL	0.378	indeterminate
Splicing
SpliceAI	Δ0.30	donor loss · deltas
Pangolin	Δ0.26	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.71, phastCons 0.98
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	19.34	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00116% 17/1,461,302 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
Admixed American	0.0117%	8,562
South Asian	0.0033%	30,344
African / African-American	0.00133%	74,952
European (non-Finnish)	0.000424%	235,926

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.Ala3029Val
Coding: c.9086C>T
MANE Select: NM_000059
dbSNP: rs80359162
Type: single nucleotide variant
Location: chr13:32379882 (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

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma BRCA2-related cancer predisposition

Similar variants

BRCA2 p.Ala3029= Likely benign ★★★ same residue
BRCA2 p.Ala3029Glu Uncertain significance ★ same residue
BRCA2 p.Ala3029Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala3029del Uncertain significance ★★ same residue
BRCA2 p.Ala3029fs 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-ala3029val (accessed [today's date]).

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