Is BRIP1 p.Val76= (c.228A>G) pathogenic?

BRIP1 p.Val76= (c.228A>G) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-09). Very rare (popmax 6.2e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Val76= (c.228A>G)?

BRIP1 p.Val76= (c.228A>G) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Val76= (c.228A>G) in the general population?

BRIP1 p.Val76= (c.228A>G) is very rare (popmax 6.2e-05%) (gnomAD).

BRIP1 p.Val76=

c.228A>G · rs2078910583 · VCV1152116

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -2.1, phastCons 0.8
Overall
CADD	1.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,936 alleles · very rare exomes 1/1,461,596 · genomes 0/152,340 · joint denominator

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.Val76=
Coding: c.228A>G
MANE Select: NM_032043
dbSNP: rs2078910583
Type: single nucleotide variant
Location: chr17:61857209 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 76: 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

Also linked: Fanconi anemia complementation group J hereditary breast carcinoma

Similar variants

BRIP1 p.Val76Ala Uncertain significance ★★ ⚠ same residue
BRIP1 p.Val76Gly Uncertain significance ★ ⚠ same residue
BRIP1 p.Val76Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Val76Leu Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>T 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-val76 (accessed [today's date]).

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