KRT6A p.Val503=
c.1509C>T · rs376504088 · VCV1627766
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0159%, nfe)
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 -13 | GERP -3.8 |
| Overall | ||
| CADD | 2.951 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0159%
European (non-Finnish) · 188/1,179,940 alleles
Filtering AF
0.014%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0133%
Overall
0.0126%
203/1,614,050 alleles · ultra-rare
exomes 186/1,461,744 · genomes 17/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0159% | 6,276 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| Admixed American | 0.005% | 20,006 |
| African / African-American | 0.004% | 25,015 |
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.Val503=
- Coding
- c.1509C>T
- MANE Select
- NM_005554
- dbSNP
- rs376504088
- Type
- single nucleotide variant
- Location
- chr12:52487906 (GRCh38)
- Gene constraint
- LOEUF 0.755 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.16 · 1 PDB
- Residue 503
- the 'tail' 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-val503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown