Is BRIP1 p.Glu512Ter (c.1534G>T) pathogenic?

BRIP1 p.Glu512Ter (c.1534G>T) is classified Pathogenic in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-16). Absent from gnomAD v4.1; Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Glu512Ter (c.1534G>T)?

BRIP1 p.Glu512Ter (c.1534G>T) is associated with Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Glu512Ter (c.1534G>T) in the general population?

BRIP1 p.Glu512Ter (c.1534G>T) is absent from gnomAD v4.1 (gnomAD).

BRIP1 p.Glu512Ter

c.1534G>T · rs1603336980 · VCV655130

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2.1, phastCons 0.95
Overall
CADD	36.0	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

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.Glu512Ter
Coding: c.1534G>T
MANE Select: NM_032043
dbSNP: rs1603336980
Type: single nucleotide variant
Location: chr17:61784364 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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.Glu512= Benign/Likely benign ★★ same residue
BRIP1 p.Glu512Gly Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu512Lys Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu512fs Pathogenic ★★ same residue
BACH1 p.Ser512Cys Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu512Ala Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>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-glu512ter (accessed [today's date]).

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