Is BRIP1 p.Leu54= (c.162A>G) pathogenic?

BRIP1 p.Leu54= (c.162A>G) is classified Likely benign in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-12). Absent from gnomAD v4.1; Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Leu54= (c.162A>G)?

BRIP1 p.Leu54= (c.162A>G) is associated with Fanconi anemia complementation group J, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Leu54= (c.162A>G) in the general population?

BRIP1 p.Leu54= (c.162A>G) is absent from gnomAD v4.1 (gnomAD).

BRIP1 p.Leu54=

c.162A>G · rs2545472235 · VCV1776775

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -0.28, phastCons 0.75
Overall
CADD	8.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRIP1
Protein: p.Leu54=
Coding: c.162A>G
MANE Select: NM_032043
dbSNP: rs2545472235
Type: single nucleotide variant
Location: chr17:61859839 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 54: 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 neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Leu54Ter Pathogenic/Likely pathogenic ★★ same residue
BRIP1 p.Leu54Ser Uncertain significance ★ ⚠ same residue
BRIP1 p.Leu54Val 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

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-leu54 (accessed [today's date]).

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