Is BRIP1 p.Val413fs (c.1236del) pathogenic?

BRIP1 p.Val413fs (c.1236del) is classified Pathogenic in BRIP1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2025-11-11). Very rare (popmax 0.000254%, nfe); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Val413fs (c.1236del)?

BRIP1 p.Val413fs (c.1236del) is associated with familial ovarian cancer, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Val413fs (c.1236del) in the general population?

BRIP1 p.Val413fs (c.1236del) is very rare (popmax 0.000254%, nfe) (gnomAD).

BRIP1 p.Val413fs

c.1236del · rs863224525 · VCV216128

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

familial ovarian cancer

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 9 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 2.1, phastCons 1
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,698 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,550 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,020
European (non-Finnish)grpmax	0.000254%	393,233

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BRIP1
Protein: p.Val413fs
Coding: c.1236del
MANE Select: NM_032043
dbSNP: rs863224525
Type: Deletion
Location: chr17:61799204 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 413: the helicase atp-binding domain

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Val413Ala Uncertain significance ★★ ⚠ same residue
BRIP1 p.Val413= Benign/Likely benign ★★ same residue
BRIP1 p.Val413Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 c.1629-3_1634del Likely pathogenic ★★ same condition
BRIP1 c.1936del Pathogenic ★★ same condition
BRIP1 c.205+1del Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.2257+2_2257+8del Likely pathogenic ★★ same condition
BRIP1 c.2370_2379+20del Likely 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-val413fs (accessed [today's date]).

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