Is BRCA2 p.Asp2811Gly (c.8432A>G) pathogenic?

BRCA2 p.Asp2811Gly (c.8432A>G) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2025-10-23). AlphaMissense: likely benign (0.1524); Very rare (popmax 0.00223%, eas); Associated with prostate cancer, hereditary.

What condition is associated with BRCA2 p.Asp2811Gly (c.8432A>G)?

BRCA2 p.Asp2811Gly (c.8432A>G) is associated with prostate cancer, hereditary, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asp2811Gly (c.8432A>G) in the general population?

BRCA2 p.Asp2811Gly (c.8432A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BRCA2 p.Asp2811Gly (c.8432A>G)?

AlphaMissense predicts likely benign (score 0.1524) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp2811Gly

c.8432A>G · rs80359090 · VCV52585

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

prostate cancer, hereditary

Computational evidence

Protein change
AlphaMissense	0.1524	likely benign
REVEL	0.568	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.00223% East Asian · 1/44,900 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,613,870 alleles · very rare exomes 15/1,461,690 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,900
European (non-Finnish)	0.00127%	78,659

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.Asp2811Gly
Coding: c.8432A>G
MANE Select: NM_000059
dbSNP: rs80359090
Type: single nucleotide variant
Location: chr13:32370502 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2811: the 'interaction with sem1' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer, hereditary — 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

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

BRCA2 p.Asp2811Val Uncertain significance ★ same residue
BRCA2 p.Asp2811= Likely benign ★ same residue
BRCA2 p.Asp2811Asn Likely benign ★ same residue
BRCA2 p.Asp2811fs Pathogenic ★ same residue
BRCA2 p.Asp2811Glu Uncertain significance ★ same residue
BRCA2 p.Asp2811His Uncertain significance ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C 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-asp2811gly (accessed [today's date]).

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