BRIP1 p.Ser46=
c.138T>C · VCV3378565
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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 1.2 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 8.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- BRIP1
- Protein
- p.Ser46=
- Coding
- c.138T>C
- MANE Select
- NM_032043
- Type
- single nucleotide variant
- Location
- chr17:61859863 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.19 · 6 PDB
- Residue 46
- the helicase atp-binding domain
Disease context
hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hereditary breast cancer (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult, Elderly
Similar variants
- BRIP1 p.Ser46Asn Uncertain significance ★★ ⚠ same residue
- BRIP1 p.Ser46Gly 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
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-ser46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown