KRTCAP2 p.Phe48Leu
c.144C>A · VCV3865993
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.291 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.37 | donor loss, 15 bp away · masked 0 · deltas |
| Pangolin | Δ0.36 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP -0.061, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 3,781 bp · p 0.55 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,890 alleles
Overall
0.000124%
2/1,614,066 alleles · very rare
exomes 1/1,461,894 · genomes 1/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,890 |
| European (non-Finnish) | 8.47e-05% | 1,180,043 |
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
- KRTCAP2
- Protein
- p.Phe48Leu
- Coding
- c.144C>A
- MANE Select
- NM_173852
- Type
- single nucleotide variant
- Location
- chr1:155172753 (GRCh38)
- Gene constraint
- LOEUF 1.04 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91 · 2 PDB
Similar variants
- KRTCAP2 p.Phe48Ser Uncertain significance ★ same residue
- KRTCAP2 c.-30G>A Uncertain significance ★ same type
- KRTCAP2 c.-35C>T Uncertain significance ★ same type
- KRTCAP2 c.-3A>G Uncertain significance ★ same type
- KRTCAP2 c.-56G>A Uncertain significance ★ same type
- KRTCAP2 c.-56G>C Uncertain significance ★ same type
- KRTCAP2 c.-57C>T Uncertain significance ★ same type
- KRTCAP2 c.-66A>G Uncertain significance ★ 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/krtcap2-p-phe48leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown