Is BRCA2 p.Pro3063fs (c.9188del) pathogenic?

BRCA2 p.Pro3063fs (c.9188del) is classified Pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-22). Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Pro3063fs (c.9188del)?

BRCA2 p.Pro3063fs (c.9188del) is associated with hereditary neoplastic syndrome (ClinVar).

BRCA2 p.Pro3063fs

c.9188del · VCV3482082

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 24 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.34	GERP -4.6, phastCons 0.23

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

Variant & gene context

Gene: BRCA2
Protein: p.Pro3063fs
Coding: c.9188del
MANE Select: NM_000059
Type: Deletion
Location: chr13:32380076 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3063: a UniProt-annotated variant site (in a patient with ovarian cancer; uncertain significance; no effect on homology-directed repair activity)

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

Similar variants

BRCA2 p.Pro3063Ser Benign/Likely benign ★★ same residue
BRCA2 p.Pro3063Arg Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Pro3063= Likely benign ★ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.8312del Pathogenic ★★★ same condition
BRCA2 c.8633-24_8634del Pathogenic ★★★ same condition
BRCA2 c.8756del Pathogenic ★★★ same condition
BRCA2 c.9403del 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-pro3063fs (accessed [today's date]).

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