Is BRCA2 p.Ala3029Glu (c.9086C>A) pathogenic?

BRCA2 p.Ala3029Glu (c.9086C>A) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). AlphaMissense: likely pathogenic (0.8811); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Ala3029Glu (c.9086C>A)?

BRCA2 p.Ala3029Glu (c.9086C>A) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ala3029Glu (c.9086C>A) in the general population?

BRCA2 p.Ala3029Glu (c.9086C>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BRCA2 p.Ala3029Glu (c.9086C>A)?

AlphaMissense predicts likely pathogenic (score 0.8811) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala3029Glu

c.9086C>A · rs80359162 · VCV2099244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8811 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,226)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.8811	likely pathogenic · top 2% in BRCA2
REVEL	0.482	indeterminate
Splicing
SpliceAI	Δ0.21	donor loss, 31 bp away · raw score · deltas
Pangolin	Δ0.23	loss · gain 0.01 · 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	18.25	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

No allele count reported in gnomAD v4.1 (AN 1,613,226). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Ala3029Glu
Coding: c.9086C>A
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

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ala3029= Likely benign ★★★ same residue
BRCA2 p.Ala3029Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala3029Val Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ala3029del Uncertain significance ★★ same residue
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>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-ala3029glu (accessed [today's date]).

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