Is BRCA2 p.Val95= (c.285A>C) pathogenic?

BRCA2 p.Val95= (c.285A>C) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-09). Very rare (popmax 0.005%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Val95= (c.285A>C)?

BRCA2 p.Val95= (c.285A>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Val95= (c.285A>C) in the general population?

BRCA2 p.Val95= (c.285A>C) is very rare (popmax 0.005%, amr) (gnomAD).

BRCA2 p.Val95=

c.285A>C · rs1057520842 · VCV380380

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP 1.1, phastCons 1
Overall
CADD	3.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,792 alleles · very rare exomes 3/1,461,548 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Val95=
Coding: c.285A>C
MANE Select: NM_000059
dbSNP: rs1057520842
Type: single nucleotide variant
Location: chr13:32319294 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Val95Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Val95Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Val95fs 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
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-val95 (accessed [today's date]).

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