BRCA1 c.4185+2del
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 1.1, phastCons 1 |
| Non-coding constraint | Z 2.10 | 1 kb window · o/e 0.84 · regional · uncalibrated |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
dbSNP / gnomAD
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- BRCA1
- Coding
- c.4185+2del
- MANE Select
- NM_007294
- dbSNP
- rs2053429850
- Type
- Deletion
- Location
- chr17:43090942 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
Similar variants
- BRCA1 c.302-2del Pathogenic ★★★ same type
- BRCA1 c.4358_4484del Pathogenic ★★★ same type
- BRCA1 c.442-22_442-13del Pathogenic ★★★ same type
- BRCA1 c.4484+1del Pathogenic ★★★ same type
- BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same type
- BRCA1 c.5278-2del Pathogenic ★★★ same type
- BRCA1 c.5333-36_5406+400del Pathogenic ★★★ same type
- BRCA1 c.5470_5477del Pathogenic ★★★ same type
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/brca1-c-4185-plus-2del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown