Is BRIP1 p.Glu1027Ala (c.3080A>C) pathogenic?

BRIP1 p.Glu1027Ala (c.3080A>C) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0975); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Glu1027Ala (c.3080A>C)?

BRIP1 p.Glu1027Ala (c.3080A>C) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group J, hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Glu1027Ala (c.3080A>C) in the general population?

BRIP1 p.Glu1027Ala (c.3080A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRIP1 p.Glu1027Ala (c.3080A>C)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

BRIP1 p.Glu1027Ala

c.3080A>C · rs863224804 · VCV216797

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	15.89	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Glu1027Ala
Coding: c.3080A>C
MANE Select: NM_032043
dbSNP: rs863224804
Type: single nucleotide variant
Location: chr17:61683966 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary breast carcinoma

Similar variants

BRIP1 p.Glu1027Gly Uncertain significance ★★ ⚠ same residue
BRIP1 p.Glu1027= Benign/Likely benign ★★ 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-glu1027ala (accessed [today's date]).

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