Is BRCA2 p.Val3079fs (c.9235del) pathogenic?

BRCA2 p.Val3079fs (c.9235del) is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 18 submitters; last evaluated 2016-09-08). Ultra-rare (popmax 0.0184%, amr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Val3079fs (c.9235del)?

BRCA2 p.Val3079fs (c.9235del) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Val3079fs (c.9235del) in the general population?

BRCA2 p.Val3079fs (c.9235del) is ultra-rare (popmax 0.0184%, amr) (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.

BRCA2 p.Val3079fs

c.9235del · rs397507422 · VCV38221

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 18 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 24 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -4.6
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Admixed American · 11/59,902 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00796%

Overall 0.000682% 11/1,613,428 alleles · ultra-rare exomes 7/1,461,328 · genomes 4/152,100 · joint denominator

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.Val3079fs
Coding: c.9235del
MANE Select: NM_000059
dbSNP: rs397507422
Type: Deletion
Location: chr13:32380124 (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

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 polydactyly

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Val3079del Uncertain significance ★ same residue
BRCA2 p.Val3079Ile Benign ★★★ same residue
BRCA2 p.Val3079Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Val3079Phe Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Val3079= Likely benign ★ same residue
BRCA2 c.316+4del Pathogenic ★★★ same condition
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del 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-val3079fs (accessed [today's date]).

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