Is BRIP1 p.Arg431= (c.1293G>A) pathogenic?

BRIP1 p.Arg431= (c.1293G>A) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-30). Very rare (popmax 0.00446%, eas); Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Arg431= (c.1293G>A)?

BRIP1 p.Arg431= (c.1293G>A) is associated with Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Arg431= (c.1293G>A) in the general population?

BRIP1 p.Arg431= (c.1293G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

BRIP1 p.Arg431=

c.1293G>A · rs2077947527 · VCV929537

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Fanconi anemia complementation group J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 0.33, phastCons 1
Overall
CADD	11.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,872 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,440 alleles · very rare

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.Arg431=
Coding: c.1293G>A
MANE Select: NM_032043
dbSNP: rs2077947527
Type: single nucleotide variant
Location: chr17:61799147 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 431: the helicase atp-binding domain

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

Disease context

Fanconi anemia complementation group J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

BRIP1 p.Arg431Lys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg431Trp Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg431Ter Pathogenic ★ same residue
BRIP1 p.Arg431Gly 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-arg431 (accessed [today's date]).

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