KRT1 p.Ala280=
c.840A>G · rs773812331 · VCV2880150
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 -3.2 | GERP -1.8 |
| Overall | ||
| CADD | 9.244 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,080 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00031%
5/1,614,198 alleles · very rare
exomes 5/1,461,848 · genomes 0/152,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,770 |
| European (non-Finnish) | 8.47e-05% | 1,180,038 |
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.Ala280=
- Coding
- c.840A>G
- MANE Select
- NM_006121
- dbSNP
- rs773812331
- Type
- single nucleotide variant
- Location
- chr12:52678190 (GRCh38)
- Gene constraint
- LOEUF 0.7 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.62 · 3 PDB
- Residue 280
- the if rod domain; the 'coil 1b' region; an α-helix
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-ala280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown