BRCA1 p.Ala1368=
c.4104A>G · rs2154258767 · VCV1200038
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.01 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.73 | GERP -3.5 |
| Overall | ||
| CADD | 6.678 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/90,630 alleles
Overall
6.85e-05%
1/1,459,818 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.Ala1368=
- Coding
- c.4104A>G
- MANE Select
- NM_007294
- dbSNP
- rs2154258767
- Type
- single nucleotide variant
- Location
- chr17:43091025 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 41.99 · 33 PDB
- Residue 1368
- a UniProt-annotated variant site (in fancs); the 'disordered' region
Similar variants
- BRCA1 p.Ala1368Thr Uncertain significance ★★ ⚠ same residue
- BRCA1 p.Ala1368Val 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-ala1368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown