Is BRCA2 c.7435+6G>A pathogenic?

BRCA2 c.7435+6G>A is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 31 submitters; last evaluated 2026-02-02). Rare (popmax 0.188%, afr); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 c.7435+6G>A?

BRCA2 c.7435+6G>A is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.7435+6G>A in the general population?

BRCA2 c.7435+6G>A is rare (popmax 0.188%, afr) (gnomAD).

BRCA2 c.7435+6G>A

rs81002852 · VCV38096

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 31 submitters

gnomAD v4.1

Rare

rare (popmax 0.188%, afr)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP -3
Non-coding constraint	Z 0.31	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	14.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% African / African-American · 141/75,012 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.0144% 232/1,613,504 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.188%	532
Middle Eastern	0.132%	756
Remaining individualsnot grpmax-eligible	0.0448%	2,231
Admixed American	0.03%	3,334
South Asian	0.0044%	22,732
European (non-Finnish)	0.0028%	35,749

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
Coding: c.7435+6G>A
MANE Select: NM_000059
dbSNP: rs81002852
Type: single nucleotide variant
Location: chr13:32355294 (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 and/or ovarian cancer — 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 hereditary breast carcinoma

Similar variants

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
BRCA2 c.476-2A>G Pathogenic ★★★ same condition
BRCA2 c.517-2A>G 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-c-7435-plus-6g-a (accessed [today's date]).

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