KRT1 p.Thr481=
c.1443C>A · rs749643681 · VCV3046666
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.056%, sas)
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 -0.71 | GERP -3.3, phastCons 0.001 |
| Overall | ||
| CADD | 10.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.056%
South Asian · 51/91,070 alleles
Filtering AF
0.0437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0394%
Overall
0.00366%
59/1,614,136 alleles · ultra-rare
exomes 59/1,461,874 · genomes 0/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.056% | 1,786 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| African / African-American | 0.00133% | 75,024 |
| European (non-Finnish) | 8.47e-05% | 1,180,027 |
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
- KRT1
- Protein
- p.Thr481=
- Coding
- c.1443C>A
- MANE Select
- NM_006121
- dbSNP
- rs749643681
- Type
- single nucleotide variant
- Location
- chr12:52676307 (GRCh38)
- Gene constraint
- LOEUF 0.7 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.62 · 3 PDB
- Residue 481
- the if rod domain; an α-helix; the 'coil 2' region
Similar variants
- KRT1 c.1255-1G>T Pathogenic ★★ same type
- KRT1 c.591+1G>C Pathogenic ★★ same type
- KRT1 p.Asn188Lys Pathogenic ★★ same type
- KRT1 p.Asn188Ser Pathogenic/Likely pathogenic ★★ same type
- KRT1 p.Ile195Asn Pathogenic/Likely pathogenic ★★ same type
- KRT1 p.Ile479Thr Pathogenic/Likely pathogenic ★★ same type
- KRT1 p.Leu187Phe Pathogenic ★★ same type
- KRT1 p.Leu485Phe Pathogenic/Likely 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/krt1-p-thr481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown