Is BRIP1 p.Gly12= (c.36G>T) pathogenic?

BRIP1 p.Gly12= (c.36G>T) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0332%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with BRIP1 p.Gly12= (c.36G>T)?

BRIP1 p.Gly12= (c.36G>T) is associated with Breast and/or ovarian cancer, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Gly12= (c.36G>T) in the general population?

BRIP1 p.Gly12= (c.36G>T) is ultra-rare (popmax 0.0332%, nfe) (gnomAD).

BRIP1 p.Gly12=

c.36G>T · rs45566938 · VCV136582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, nfe)

Conditions

Breast and/or ovarian cancer

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 -0.13	GERP -3.5, phastCons 0.46
Overall
CADD	7.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% European (non-Finnish) · 391/1,179,378 alleles

Filtering AF 0.0304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.026% 420/1,613,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0332%	3,016
Middle Eastern	0.0329%	3,040
Admixed American	0.025%	3,998
Remaining individualsnot grpmax-eligible	0.0176%	5,677
Finnishnot grpmax-eligible	0.00156%	63,966

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.Gly12=
Coding: c.36G>T
MANE Select: NM_032043
dbSNP: rs45566938
Type: single nucleotide variant
Location: chr17:61861504 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 12: the helicase atp-binding domain

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Gly12Ala Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly12Arg Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly12Glu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly12Val Uncertain significance ★★ ⚠ same residue
BRIP1 p.Gly12_Val13insTer Pathogenic/Likely pathogenic ★★ same residue
BRIP1 p.Gly12fs Pathogenic ★ 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-gly12 (accessed [today's date]).

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