Is BRIP1 p.Glu1027Asp (c.3081G>C) pathogenic?

BRIP1 p.Glu1027Asp (c.3081G>C) is classified Uncertain significance in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-31). AlphaMissense: likely benign (0.1054); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Glu1027Asp (c.3081G>C)?

BRIP1 p.Glu1027Asp (c.3081G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Glu1027Asp (c.3081G>C) in the general population?

BRIP1 p.Glu1027Asp (c.3081G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BRIP1 p.Glu1027Asp (c.3081G>C)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

BRIP1 p.Glu1027Asp

c.3081G>C · rs777660106 · VCV2449918

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -7.09	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 0.25	GERP 0.15, phastCons 0.91
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	8.051	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,870 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.Glu1027Asp
Coding: c.3081G>C
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

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

Similar variants

BRIP1 p.Glu1027Gly Uncertain significance ★★ ⚠ same residue
BRIP1 p.Glu1027= Benign/Likely benign ★★ same residue
BRIP1 p.Glu1027Ala Conflicting classifications of pathogenicity ★ ⚠ 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>G 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-glu1027asp (accessed [today's date]).

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