BRCA1 p.Leu1605=
c.4815G>A · rs1060504589 · VCV415603
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
2
hereditary neoplastic syndrome
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 4.9 | GERP 0.42, phastCons 1 |
| Overall | ||
| CADD | 1.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,980 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000137%
2/1,461,828 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.Leu1605=
- Coding
- c.4815G>A
- MANE Select
- NM_007294
- dbSNP
- rs1060504589
- Type
- single nucleotide variant
- Location
- chr17:43071099 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
- Residue 1605
- a UniProt-annotated variant site (in fancs)
Similar variants
- BRCA1 p.Leu1605Met Uncertain significance ★★ ⚠ same residue
- BRCA1 p.Leu1605Ser Uncertain significance ★★ ⚠ same residue
- BRCA1 p.Leu1605Phe Likely benign ★ ⚠ same residue
- BRCA1 p.Leu1605fs Pathogenic/Likely pathogenic ★★ same residue
- BRCA1 p.Leu1605Val Uncertain significance ⚠ same residue
- BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
- BRCA1 c.135-1G>T Pathogenic ★★★ same condition
- BRCA1 c.212+1G>A 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/brca1-p-leu1605 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown