Is BRIP1 p.Glu1027= (c.3081G>A) pathogenic?

BRIP1 p.Glu1027= (c.3081G>A) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-09). Ultra-rare (popmax 0.0198%, sas); Associated with Fanconi anemia complementation group J.

What condition is associated with BRIP1 p.Glu1027= (c.3081G>A)?

BRIP1 p.Glu1027= (c.3081G>A) is associated with Fanconi anemia complementation group J, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Glu1027= (c.3081G>A) in the general population?

BRIP1 p.Glu1027= (c.3081G>A) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

BRIP1 p.Glu1027=

c.3081G>A · rs777660106 · VCV491461

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

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 0.25	GERP 0.15, phastCons 0.91
Overall
CADD	1.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,080 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.0013% 19/1,461,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,060
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Glu1027=
Coding: c.3081G>A
MANE Select: NM_032043
dbSNP: rs777660106
Type: single nucleotide variant
Location: chr17:61683965 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 1027: the 'interaction with brca1' region; the 'disordered' region

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.Glu1027Gly Uncertain significance ★★ ⚠ same residue
BRIP1 p.Glu1027Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Glu1027Asp Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu1027Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Glu1027Lys Conflicting classifications of pathogenicity ★ ⚠ 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

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-glu1027 (accessed [today's date]).

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