Is BRCA2 p.Ala2351Gly (c.7052C>G) pathogenic?

BRCA2 p.Ala2351Gly (c.7052C>G) is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 25 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1313); Rare (popmax 0.21%, eas); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 p.Ala2351Gly (c.7052C>G)?

BRCA2 p.Ala2351Gly (c.7052C>G) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Ala2351Gly (c.7052C>G) in the general population?

BRCA2 p.Ala2351Gly (c.7052C>G) is rare (popmax 0.21%, eas) (gnomAD).

What do computational predictors say about BRCA2 p.Ala2351Gly (c.7052C>G)?

AlphaMissense predicts likely benign (score 0.1313) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala2351Gly

c.7052C>G · rs80358932 · VCV38081

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 25 submitters

AlphaMissense

likely benign

0.1313 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.21%, eas)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1313	likely benign
REVEL	0.405	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP -2.1, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	13.25	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

Grpmax group 0.21% East Asian · 94/44,840 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.00719% 116/1,613,572 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.21%	477
Remaining individualsnot grpmax-eligible	0.032%	3,124
European (non-Finnish)	0.00017%	589,821

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.Ala2351Gly
Coding: c.7052C>G
MANE Select: NM_000059
dbSNP: rs80358932
Type: single nucleotide variant
Location: chr13:32354905 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2351: the 'interaction with fancd2' region

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 cancer Fanconi anemia complementation group D1 breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRCA2 p.Ala2351Pro Uncertain significance ★★ same residue
BRCA2 p.Ala2351Val Uncertain significance ★★ ⚠ same residue
BRCA2 p.Ala2351Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala2351Thr Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ala2351= Likely benign ★ 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-ala2351gly (accessed [today's date]).

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