Is BRCA2 p.Phe1030Val (c.3088T>G) pathogenic?

BRCA2 p.Phe1030Val (c.3088T>G) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1847); Very rare (popmax 0.00334%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Phe1030Val (c.3088T>G)?

BRCA2 p.Phe1030Val (c.3088T>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Phe1030Val (c.3088T>G) in the general population?

BRCA2 p.Phe1030Val (c.3088T>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about BRCA2 p.Phe1030Val (c.3088T>G)?

AlphaMissense predicts likely benign (score 0.1847) — an in-silico prediction, not a clinical call.

BRCA2 p.Phe1030Val

c.3088T>G · rs80358554 · VCV51397

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1847	likely benign
REVEL	0.3	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP -1.5, phastCons 0.59
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	16.58	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 0.00334% Admixed American · 2/59,866 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,612,770 alleles · very rare exomes 11/1,460,608 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,933
European (non-Finnish)	0.000848%	117,932

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.Phe1030Val
Coding: c.3088T>G
MANE Select: NM_000059
dbSNP: rs80358554
Type: single nucleotide variant
Location: chr13:32337443 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1030: the 'interaction with rad51' region

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 breast-ovarian cancer, familial, susceptibility to, 2

Similar variants

BRCA2 p.Phe1030Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Phe1030Ser Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Phe1030= Likely benign ★ same residue
BRCA2 p.Phe1030fs 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

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-phe1030val (accessed [today's date]).

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