Is BRCA2 p.Thr3195fs (c.9581dup) pathogenic?

BRCA2 p.Thr3195fs (c.9581dup) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-12). Ultra-rare (gnomAD MAF 3.358e-06); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Thr3195fs (c.9581dup)?

BRCA2 p.Thr3195fs (c.9581dup) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, hereditary breast carcinoma (ClinVar).

How common is BRCA2 p.Thr3195fs (c.9581dup) in the general population?

BRCA2 p.Thr3195fs (c.9581dup) is ultra-rare (gnomAD MAF 3.358e-06) (gnomAD).

BRCA2 p.Thr3195fs

c.9581dup · rs80359771 · VCV2025823

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 3.358e-06)

Conditions

hereditary neoplastic syndrome

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 26 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 1.2, phastCons 0.21

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000336% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BRCA2
Protein: p.Thr3195fs
Coding: c.9581dup
MANE Select: NM_000059
dbSNP: rs80359771
Type: Duplication
Location: chr13:32396973 (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 hereditary breast carcinoma

Similar variants

BRCA2 p.Thr3195Ser Uncertain significance ★★ ⚠ same residue
BRCA2 p.Thr3195Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Thr3195Asn Uncertain significance ★ ⚠ same residue
BRCA2 p.Thr3195Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.1448_1451dupCAGT Pathogenic ★★★ same condition
BRCA2 c.6081dupA Pathogenic ★★★ same condition
BRCA2 c.6396dupA Pathogenic ★★★ same condition
BRCA2 c.6528_6535dup 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-thr3195fs (accessed [today's date]).

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