Is BRIP1 p.Leu373= (c.1119A>G) pathogenic?

BRIP1 p.Leu373= (c.1119A>G) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-23). Very rare (popmax 8.48e-05%, nfe); Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Leu373= (c.1119A>G)?

BRIP1 p.Leu373= (c.1119A>G) is associated with Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Leu373= (c.1119A>G) in the general population?

BRIP1 p.Leu373= (c.1119A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

BRIP1 p.Leu373=

c.1119A>G · rs2545151378 · VCV2939216

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Fanconi anemia complementation group J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.053	GERP 2, phastCons 0.89
Overall
CADD	7.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,508 alleles

Overall 6.84e-05% 1/1,461,274 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.Leu373=
Coding: c.1119A>G
MANE Select: NM_032043
dbSNP: rs2545151378
Type: single nucleotide variant
Location: chr17:61801274 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 373: 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.Leu373Pro 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
BRIP1 c.1340+1G>A Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>A Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>C 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-leu373 (accessed [today's date]).

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