Is BRCA2 p.Asp2312Val (c.6935A>T) pathogenic?

BRCA2 p.Asp2312Val (c.6935A>T) is classified Benign in BRCA2 (ClinVar, Expert panel, 26 submitters; last evaluated 2019-06-18). AlphaMissense: likely benign (0.2692); Rare (popmax 0.204%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Asp2312Val (c.6935A>T)?

BRCA2 p.Asp2312Val (c.6935A>T) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Asp2312Val (c.6935A>T) in the general population?

BRCA2 p.Asp2312Val (c.6935A>T) is rare (popmax 0.204%, sas) (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.Asp2312Val (c.6935A>T)?

AlphaMissense predicts likely benign (score 0.2692) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp2312Val

c.6935A>T · rs80358916 · VCV52220

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 26 submitters

AlphaMissense

likely benign

0.2692 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.204%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
AlphaMissense	0.2692	likely benign
REVEL	0.894	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Pangolin	Δ0.33	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	32.0	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 0.204% South Asian · 183/89,892 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.0141% 220/1,558,374 alleles · rare exomes 209/1,406,156 · genomes 11/152,218 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.204%	491
Middle Eastern	0.0339%	2,952
Remaining individualsnot grpmax-eligible	0.0165%	6,066
African / African-American	0.00271%	36,864
European (non-Finnish)	0.00195%	51,360
Admixed American	0.00167%	59,820

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.Asp2312Val
Coding: c.6935A>T
MANE Select: NM_000059
dbSNP: rs80358916
Type: single nucleotide variant
Location: chr13:32344651 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2312: the 'interaction with hsf2bp' region; an α-helix

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 medulloblastoma prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 glioma susceptibility 3 pancreatic cancer, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma BRCA2-related cancer predisposition

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asp2312Glu Uncertain significance ★ same residue
BRCA2 p.Asp2312Gly Uncertain significance ★ ⚠ 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
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>A Pathogenic ★★★ same condition
BRCA2 c.475+1G>T 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-asp2312val (accessed [today's date]).

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