Is BRIP1 p.Asp1189= (c.3567T>C) pathogenic?

BRIP1 p.Asp1189= (c.3567T>C) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0424%, eas); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Asp1189= (c.3567T>C)?

BRIP1 p.Asp1189= (c.3567T>C) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Asp1189= (c.3567T>C) in the general population?

BRIP1 p.Asp1189= (c.3567T>C) is ultra-rare (popmax 0.0424%, eas) (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.Asp1189=

c.3567T>C · rs764848326 · VCV185173

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

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 0.6	GERP -1.6
Overall
CADD	4.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,836 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.0013% 21/1,613,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0424%	2,360
Admixed American	0.00167%	59,978
European (non-Finnish)	8.48e-05%	1,179,786

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.Asp1189=
Coding: c.3567T>C
MANE Select: NM_032043
dbSNP: rs764848326
Type: single nucleotide variant
Location: chr17:61683479 (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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Asp1189Asn 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
BRIP1 c.1141-2A>T Likely pathogenic ★★ same condition
BRIP1 c.1340+1G>A Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>A Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>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-asp1189 (accessed [today's date]).

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