KRT6A p.Ala262=
c.786A>G · rs373623240 · VCV2919176
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0426%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP 0.78 |
| Overall | ||
| CADD | 9.378 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0426%
African / African-American · 32/75,060 alleles
Filtering AF
0.031%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0271%
Overall
0.00223%
36/1,613,992 alleles · ultra-rare
exomes 20/1,461,668 · genomes 16/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0426% | 2,346 |
| Admixed American | 0.00333% | 30,009 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,246 |
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
- KRT6A
- Protein
- p.Ala262=
- Coding
- c.786A>G
- MANE Select
- NM_005554
- dbSNP
- rs373623240
- Type
- single nucleotide variant
- Location
- chr12:52491142 (GRCh38)
- Gene constraint
- LOEUF 0.755 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.16 · 1 PDB
- Residue 262
- the if rod domain; the 'coil 1b' region
Similar variants
- KRT6A c.1460-1G>C Pathogenic/Likely pathogenic ★★ same type
- KRT6A p.Arg164Cys Pathogenic/Likely pathogenic ★★ same type
- KRT6A p.Asn171Lys Pathogenic ★★ same type
- KRT6A p.Asn171Ser Pathogenic ★★ same type
- KRT6A p.Glu163Lys Pathogenic ★★ same type
- KRT6A p.Glu472Lys Pathogenic/Likely pathogenic ★★ same type
- KRT6A p.Ile462Asn Pathogenic/Likely pathogenic ★★ same type
- KRT6A p.Leu170Phe 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/krt6a-p-ala262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown