KRT5 p.Ala398=
c.1194C>T · rs768794468 · VCV309561
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0983%, amr)
Conditions
1
epidermolysis bullosa simplex
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 -16 | |
| Overall | ||
| CADD | 0.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0983%
Admixed American · 59/59,990 alleles
Filtering AF
0.0783%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0709%
Overall
0.00489%
79/1,613,902 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0983% | 1,017 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| South Asian | 0.00439% | 22,770 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- KRT5
- Protein
- p.Ala398=
- Coding
- c.1194C>T
- MANE Select
- NM_000424
- dbSNP
- rs768794468
- Type
- single nucleotide variant
- Location
- chr12:52517131 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 68.86 · 2 PDB
- Residue 398
- the if rod domain; an α-helix; a UniProt-annotated variant site (in ddd1); the 'coil 2' region
Similar variants
- KRT5 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same condition
- KRT5 p.Ala428Val Pathogenic/Likely pathogenic ★★ same condition
- KRT5 p.Glu170Lys Pathogenic ★★ same condition
- KRT5 p.Glu466Gln Pathogenic/Likely pathogenic ★★ same condition
- KRT5 p.Glu477Lys Pathogenic ★★ same condition
- KRT5 p.Leu196Pro Pathogenic/Likely pathogenic ★★ same condition
- KRT5 p.Leu463Pro Pathogenic ★★ same condition
- KRT5 p.Pro25Leu Pathogenic ★★ 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/krt5-p-ala398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown