KRT8 p.Phe452=
c.1356C>T · rs542852966 · VCV3025808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.186%, sas)
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 -0.57 | GERP -4.7 |
| Overall | ||
| CADD | 5.506 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.186%
South Asian · 169/91,022 alleles
Filtering AF
0.163%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.0122%
195/1,598,626 alleles · rare
exomes 184/1,446,272 · genomes 11/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.186% | 539 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,386 |
| European (non-Finnish) | 0.0017% | 58,995 |
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
- KRT8
- Protein
- p.Phe452=
- Coding
- c.1356C>T
- MANE Select
- NM_002273
- dbSNP
- rs542852966
- Type
- single nucleotide variant
- Location
- chr12:52897524 (GRCh38)
- Gene constraint
- LOEUF 0.79 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.13 · 3 PDB
- Residue 452
- the 'tail' region
Similar variants
- KRT8 p.Lys464Asn Uncertain significance ★★ ⚠ same type
- KRT8 c.-4T>C Benign ★★ same type
- KRT8 p.Ala333= Benign ★★ same type
- KRT8 p.Arg341His Benign ★★ same type
- KRT8 p.Gly434Ser Benign ★★ same type
- KRT8 p.Gly62Cys Benign/Likely benign ★★ ⚠ same type
- KRT8 p.Ile63Val Benign/Likely benign ★★ ⚠ same type
- KRT8 p.Tyr54His Benign/Likely benign ★★ ⚠ 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/krt8-p-phe452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown