KRT1 p.Ile412=
c.1236C>T · rs137978741 · VCV765611
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0533%, afr)
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 -7.8 | GERP -4.3 |
| Overall | ||
| CADD | 0.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0533%
African / African-American · 40/75,064 alleles
Filtering AF
0.0401%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0356%
Overall
0.00632%
102/1,613,612 alleles · ultra-rare
exomes 72/1,461,308 · genomes 30/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0533% | 1,877 |
| Admixed American | 0.02% | 5,003 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,500 |
| European (non-Finnish) | 0.00347% | 28,781 |
| Finnishnot grpmax-eligible | 0.00315% | 31,726 |
| South Asian | 0.0011% | 91,064 |
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.Ile412=
- Coding
- c.1236C>T
- MANE Select
- NM_006121
- dbSNP
- rs137978741
- Type
- single nucleotide variant
- Location
- chr12:52677077 (GRCh38)
- Gene constraint
- LOEUF 0.7 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.62 · 3 PDB
- Residue 412
- 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-ile412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown