KRT5 p.Glu252=
c.756A>G · VCV4916983
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.679 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.46 | phastCons 0.032 |
| Overall | ||
| CADD | 9.246 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,180,042 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00155%
25/1,614,096 alleles · very rare
exomes 23/1,461,888 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00195% | 51,306 |
| African / African-American | 0.00133% | 74,928 |
| South Asian | 0.0011% | 91,084 |
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.Glu252=
- Coding
- c.756A>G
- MANE Select
- NM_000424
- Type
- single nucleotide variant
- Location
- chr12:52518960 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 68.86 · 2 PDB
- Residue 252
- the if rod domain; a UniProt-annotated variant site (in ddd1); the 'coil 1b' 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-glu252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown