KRT5 p.Phe219=
c.657C>T · rs750787121 · VCV2713861
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.076 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -11 | |
| Overall | ||
| CADD | 0.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,082 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00434%
70/1,614,064 alleles · ultra-rare
exomes 59/1,461,890 · genomes 11/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,506 |
| Admixed American | 0.01% | 9,999 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
| European (non-Finnish) | 0.00364% | 27,443 |
| African / African-American | 0.00267% | 37,461 |
| East Asian | 0.00223% | 44,896 |
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.Phe219=
- Coding
- c.657C>T
- MANE Select
- NM_000424
- dbSNP
- rs750787121
- Type
- single nucleotide variant
- Location
- chr12:52519059 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 68.86 · 2 PDB
- Residue 219
- the if rod domain; a UniProt-annotated variant site (in ddd1); the 'linker 1' region
Similar variants
- 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
- KRT5 p.Asn176Ser Pathogenic/Likely pathogenic ★★ same type
- KRT5 p.Asn177Ser 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-phe219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown