KRT2 p.Phe53=
c.159C>T · VCV4803694
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.177%, amr)
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 -2.7 | GERP -4.1 |
| Overall | ||
| CADD | 3.025 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.177%
Admixed American · 106/59,994 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.139%
Overall
0.0347%
560/1,612,994 alleles · rare
exomes 516/1,460,832 · genomes 44/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.177% | 566 |
| European (non-Finnish) | 0.0348% | 2,877 |
| South Asian | 0.0198% | 5,058 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| African / African-American | 0.0147% | 6,820 |
| East Asian | 0.00669% | 14,957 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
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
- KRT2
- Protein
- p.Phe53=
- Coding
- c.159C>T
- MANE Select
- NM_000423
- Type
- single nucleotide variant
- Location
- chr12:52651984 (GRCh38)
- Gene constraint
- LOEUF 1 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.38
- Residue 53
- the 'head' region
Similar variants
- KRT2 p.Phe53Leu Uncertain significance ★ ⚠ same residue
- KRT2 p.Glu487Lys Pathogenic ★★ same type
- KRT2 p.Glu488Lys Likely pathogenic ★★ same type
- KRT2 p.Arg544Gln Uncertain significance ★★ ⚠ same type
- KRT2 p.Asn498Ile Uncertain significance ★★ ⚠ same type
- KRT2 c.1122+16G>A Benign ★★ same type
- KRT2 c.1248+22C>T Benign ★★ same type
- KRT2 c.1249-4A>G 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/krt2-p-phe53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown