Is BRIP1 p.Glu879= (c.2637A>G) pathogenic?

BRIP1 p.Glu879= (c.2637A>G) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-04). Common (popmax 90.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Glu879= (c.2637A>G)?

BRIP1 p.Glu879= (c.2637A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, ovarian cancer (ClinVar).

BRIP1 p.Glu879=

Q: How common is BRIP1 p.Glu879= (c.2637A>G) in the general population?

BRIP1 p.Glu879= (c.2637A>G) is common (popmax 90.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2637A>G · rs4986765 · VCV183703

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

gnomAD v4.1

Common

common (popmax 90.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary neoplastic syndrome

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 -0.2	GERP -2.1, phastCons 0.15
Overall
CADD	5.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.9% African / African-American · 68,125/74,984 alleles

Filtering AF 90.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 90%

Overall 68.7% 1,108,498/1,613,482 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	90.9%	1
East Asian	89.3%	1
Admixed American	85.3%	1
Middle Eastern	78.5%	1
Remaining individualsnot grpmax-eligible	70.4%	1
South Asian	70.3%	1
Ashkenazi Jewishnot grpmax-eligible	69.5%	1
European (non-Finnish)	66.3%	2
Finnishnot grpmax-eligible	51.5%	2
Amishnot grpmax-eligible	51%	2

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.Glu879=
Coding: c.2637A>G
MANE Select: NM_032043
dbSNP: rs4986765
Type: single nucleotide variant
Location: chr17:61686104 (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

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

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

Similar variants

BRIP1 p.Glu879Gly Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu879Lys Uncertain significance ★ ⚠ same residue
BRIP1 p.Glu879Val Uncertain significance ★ same residue
BRIP1 p.Glu879_Ser880= 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-glu879 (accessed [today's date]).

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