Is BRCA2 p.Ala3029= (c.9087G>A) pathogenic?

BRCA2 p.Ala3029= (c.9087G>A) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 12 submitters; last evaluated 2017-06-29). Ultra-rare (popmax 0.0494%, mid); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ala3029= (c.9087G>A)?

BRCA2 p.Ala3029= (c.9087G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ala3029= (c.9087G>A) in the general population?

BRCA2 p.Ala3029= (c.9087G>A) is ultra-rare (popmax 0.0494%, mid) (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.

BRCA2 p.Ala3029=

c.9087G>A · rs368576266 · VCV136572

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.52	GERP -4.9, phastCons 0.9
Overall
CADD	3.366	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% Middle Eastern · 3/6,078 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00716%

Overall 0.00415% 67/1,613,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,026
Finnishnot grpmax-eligible	0.0203%	4,917
African / African-American	0.00535%	18,709
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	0.00356%	28,087
Admixed American	0.00167%	59,936
South Asian	0.0011%	91,014

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.Ala3029=
Coding: c.9087G>A
MANE Select: NM_000059
dbSNP: rs368576266
Type: single nucleotide variant
Location: chr13:32379883 (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-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ala3029Glu Uncertain significance ★ 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 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-ala3029 (accessed [today's date]).

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