Is BRIP1 p.Phe366fs (c.1095_1096del) pathogenic?

BRIP1 p.Phe366fs (c.10951096del) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Phe366fs (c.1095_1096del)?

BRIP1 p.Phe366fs (c.1095_1096del) is associated with hereditary neoplastic syndrome (ClinVar).

BRIP1 p.Phe366fs

c.1095_1096del · VCV4631063

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 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

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

Variant & gene context

Gene: BRIP1
Protein: p.Phe366fs
Coding: c.1095_1096del
MANE Select: NM_032043
Type: Microsatellite
Location: chr17:61801297 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 366: the helicase atp-binding domain

Full BRIP1 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

BRIP1 p.Phe366Leu Uncertain significance ★★ ⚠ same residue
BRIP1 c.1340+2_1340+5del Likely pathogenic ★★ same condition
BRIP1 c.2492_2492+3del Likely pathogenic ★★ same condition
BRIP1 p.Ala402fs Pathogenic ★★ same condition
BRIP1 p.Asn97fs Pathogenic ★★ same condition
BRIP1 p.Gln376fs Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Glu751fs Pathogenic ★★ same condition
BRIP1 p.Ile902fs 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/brip1-p-phe366fs (accessed [today's date]).

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