BRIP1 p.Trp1002fs
c.3004_3005insTGACAGCT · rs763443434 · VCV186335
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (20 of 20) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 26.3 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Trp1002fs
- Coding
- c.3004_3005insTGACAGCT
- MANE Select
- NM_032043
- dbSNP
- rs763443434
- Type
- Insertion
- Location
- chr17:61684041 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.19 · 6 PDB
- Residue 1002
- the 'interaction with brca1' region
Disease context
hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Fanconi anemia complementation group Jhereditary neoplastic syndrome
For Hereditary breast cancer (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial
- Onset
- Adult, Elderly
Similar variants
- BRIP1 p.Trp1002Cys Uncertain significance ★★ ⚠ same residue
- BRIP1 p.Trp1002Ser Uncertain significance ★ ⚠ same residue
- BRIP1 p.Trp1002Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
- BRIP1 p.Asp566_Lys567insIleSerAsnTer Pathogenic ★★ same condition
- BRIP1 p.Leu340fs Pathogenic/Likely pathogenic ★★ same condition
- BRIP1 p.Pro619fs Pathogenic/Likely pathogenic ★★ same condition
- BRIP1 p.Ser215fs Pathogenic ★★ same condition
- BRIP1 p.Val864fs 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-trp1002fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown