BRCA1 p.Leu182=
c.544T>C · VCV4822953
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.54e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.34 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.7 | GERP -5.2, phastCons 0.007 |
| Overall | ||
| CADD | 2.249 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.54e-05%
European (non-Finnish) · 1/1,171,096 alleles
Overall
6.89e-05%
1/1,451,922 alleles · very rare
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
- BRCA1
- Protein
- p.Leu182=
- Coding
- c.544T>C
- MANE Select
- NM_007294
- Type
- single nucleotide variant
- Location
- chr17:43099778 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
Similar variants
- BRCA1 p.Leu182Met Uncertain significance ★★ ⚠ same residue
- BRCA1 p.Leu182Phe Uncertain significance ★★ ⚠ same residue
- BRCA1 c.134+3A>T Likely pathogenic ★★★ same type
- BRCA1 c.135-1G>T Pathogenic ★★★ same type
- BRCA1 c.212+1G>A Pathogenic ★★★ same type
- BRCA1 c.212+1G>T Pathogenic ★★★ same type
- BRCA1 c.212+3A>G Pathogenic ★★★ same type
- BRCA1 c.213-12A>G 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-p-leu182 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown