Is BRCA2 c.8331+16C>G pathogenic?

BRCA2 c.8331+16C>G is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-11-17). Very rare (popmax 0.0083%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 c.8331+16C>G?

BRCA2 c.8331+16C>G is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.8331+16C>G in the general population?

BRCA2 c.8331+16C>G is very rare (popmax 0.0083%, nfe) (gnomAD).

BRCA2 c.8331+16C>G

rs730881595 · VCV182298

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0083%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.6
Non-coding constraint	Z 0.81	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	2.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0083% European (non-Finnish) · 97/1,168,072 alleles

Filtering AF 0.00696% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0064%

Overall 0.00619% 99/1,600,376 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0083%	12,042
Admixed American	0.00167%	59,848
African / African-American	0.00134%	74,636

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.8331+16C>G
MANE Select: NM_000059
dbSNP: rs730881595
Type: single nucleotide variant
Location: chr13:32363549 (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 breast-ovarian cancer, familial, susceptibility to, 2

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-8331-plus-16c-g (accessed [today's date]).

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