Is BRIP1 p.Asp1141= (c.3423T>C) pathogenic?

BRIP1 p.Asp1141= (c.3423T>C) is classified Likely benign in BRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-14). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Asp1141= (c.3423T>C)?

BRIP1 p.Asp1141= (c.3423T>C) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Asp1141= (c.3423T>C) in the general population?

BRIP1 p.Asp1141= (c.3423T>C) is very rare (popmax 8.48e-05%, 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.Asp1141=

c.3423T>C · rs2144076602 · VCV1099135

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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 0.13	GERP -3
Overall
CADD	1.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,888 alleles

Overall 6.2e-05% 1/1,612,320 alleles · very rare exomes 1/1,460,092 · genomes 0/152,228 · joint denominator

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.Asp1141=
Coding: c.3423T>C
MANE Select: NM_032043
dbSNP: rs2144076602
Type: single nucleotide variant
Location: chr17:61683623 (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

For Hereditary breast cancer (Orphanet):

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

Similar variants

BRIP1 p.Asp1141Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Asp1141Val Uncertain significance ★ ⚠ same residue
BRIP1 p.Asp1141fs Uncertain significance ★ same residue
BRIP1 p.Asp1141Gly 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

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-asp1141 (accessed [today's date]).

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