Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.21%, nfe)
Conditions
2
epidermolytic ichthyosis
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 -20 | GERP -3.4 |
| Overall | ||
| CADD | 0.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.21%
European (non-Finnish) · 14,311/1,180,028 alleles
Filtering AF
1.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.19%
Overall
0.982%
15,858/1,614,192 alleles · low-frequency
exomes 14,818/1,461,872 · genomes 1,040/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.21% | 82 |
| Remaining individualsnot grpmax-eligible | 0.897% | 111 |
| Admixed American | 0.653% | 153 |
| Ashkenazi Jewishnot grpmax-eligible | 0.608% | 164 |
| Finnishnot grpmax-eligible | 0.306% | 327 |
| African / African-American | 0.22% | 455 |
| South Asian | 0.0538% | 1,859 |
| Middle Eastern | 0.033% | 3,031 |
| East Asian | 0.00446% | 22,445 |
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.Ser254=
- Coding
- c.762G>A
- MANE Select
- NM_006121
- dbSNP
- rs2741155
- Type
- single nucleotide variant
- Location
- chr12:52678586 (GRCh38)
- Gene constraint
- LOEUF 0.7 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.62 · 3 PDB
- Residue 254
- the if rod domain; the 'coil 1b' region; an α-helix
Similar variants
- KRT1 p.Ser254Leu Likely benign ★ same residue
- KRT1 c.1255-1G>T Pathogenic ★★ same condition
- KRT1 p.Asn188Lys Pathogenic ★★ same condition
- KRT1 p.Leu485Phe Pathogenic/Likely pathogenic ★★ same condition
- KRT1 p.Arg86His Uncertain significance ★★ ⚠ same condition
- KRT1 p.Gly556Ser Uncertain significance ★★ ⚠ same condition
- KRT1 c.1511-11T>C Benign/Likely benign ★★ same condition
- KRT1 c.592-8G>A Benign/Likely benign ★★ 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/krt1-p-ser254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown