KRT5 p.Arg559=
c.1677A>T · rs1469765298 · VCV737820
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0271%, mid)
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 -0.64 | |
| Overall | ||
| CADD | 1.938 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0271%
Middle Eastern · 1/3,690 alleles
Filtering AF
0.00333%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0029%
Overall
0.00426%
39/914,756 alleles · ultra-rare
exomes 38/838,470 · genomes 1/76,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0271% | 3,690 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00578% | 17,298 |
| Finnishnot grpmax-eligible | 0.00573% | 17,447 |
| East Asian | 0.00566% | 17,668 |
| African / African-American | 0.00502% | 19,920 |
| European (non-Finnish) | 0.00464% | 21,538 |
| South Asian | 0.00162% | 61,746 |
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.Arg559=
- Coding
- c.1677A>T
- MANE Select
- NM_000424
- dbSNP
- rs1469765298
- Type
- single nucleotide variant
- Location
- chr12:52515038 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 68.86 · 2 PDB
- Residue 559
- a UniProt-annotated variant site (found in a patient with ebs with an unspecified subtype; likely pathogenic); a UniProt-annotated variant site (in ddd1); the 'tail' region
Similar variants
- KRT5 p.Arg559Gln Uncertain significance ★★ ⚠ same residue
- KRT5 p.Arg559Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
- KRT5 c.555+1G>A Pathogenic ★★ same type
- KRT5 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same type
- KRT5 p.Ala428Val Pathogenic/Likely pathogenic ★★ same type
- KRT5 p.Arg165Ser Pathogenic ★★ same type
- KRT5 p.Arg331Cys Pathogenic/Likely pathogenic ★★ same type
- KRT5 p.Arg331His 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/krt5-p-arg559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown