Is BRIP1 p.Arg762= (c.2286T>C) pathogenic?

BRIP1 p.Arg762= (c.2286T>C) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-03). Rare (popmax 0.542%, afr); Associated with Breast and/or ovarian cancer.

What condition is associated with BRIP1 p.Arg762= (c.2286T>C)?

BRIP1 p.Arg762= (c.2286T>C) is associated with Breast and/or ovarian cancer, breast cancer, ovarian cancer (ClinVar).

How common is BRIP1 p.Arg762= (c.2286T>C) in the general population?

BRIP1 p.Arg762= (c.2286T>C) is rare (popmax 0.542%, afr) (gnomAD).

BRIP1 p.Arg762=

c.2286T>C · rs61754141 · VCV136575

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

gnomAD v4.1

Rare

rare (popmax 0.542%, afr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.088	GERP 0.65, phastCons 0.12
Overall
CADD	8.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.542% African / African-American · 407/75,048 alleles

Filtering AF 0.499% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.482%

Overall 0.038% 614/1,614,018 alleles · rare exomes 371/1,461,700 · genomes 243/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.542%	184
Middle Eastern	0.132%	758
Admixed American	0.102%	984
Remaining individualsnot grpmax-eligible	0.056%	1,786
European (non-Finnish)	0.00856%	11,682
South Asian	0.0022%	45,541

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.Arg762=
Coding: c.2286T>C
MANE Select: NM_032043
dbSNP: rs61754141
Type: single nucleotide variant
Location: chr17:61743106 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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

Similar variants

BRIP1 p.Arg762Cys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg762His Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg762Leu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Arg762Pro Uncertain significance ★ ⚠ same residue
BRIP1 p.Arg762Tyr Uncertain significance ★★ 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-arg762 (accessed [today's date]).

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