Is BRIP1 p.Ala1030= (c.3090C>T) pathogenic?

BRIP1 p.Ala1030= (c.3090C>T) is classified Benign in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.000254%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Ala1030= (c.3090C>T)?

BRIP1 p.Ala1030= (c.3090C>T) is associated with hereditary breast carcinoma (ClinVar).

How common is BRIP1 p.Ala1030= (c.3090C>T) in the general population?

BRIP1 p.Ala1030= (c.3090C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

BRIP1 p.Ala1030=

c.3090C>T · VCV3379353

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

hereditary breast carcinoma

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 -0.1	GERP -3.9
Overall
CADD	1.276	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,032 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,876 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.Ala1030=
Coding: c.3090C>T
MANE Select: NM_032043
Type: single nucleotide variant
Location: chr17:61683956 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 1030: 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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRIP1 p.Ala1030Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Ala1030_Ser1032dup Uncertain significance ★★ same residue
BRIP1 p.Ala1030Thr Uncertain significance ★ ⚠ same residue
BRIP1 p.Ala1030Gly Likely benign ★ 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

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-ala1030 (accessed [today's date]).

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