KRTCAP2 p.Pro125Ser
c.373C>T · rs908331937 · VCV2466958
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00356%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.089 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.6 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 3,781 bp · p 0.55 · regional, not allelic |
| Overall | ||
| CADD | 22.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
European (non-Finnish) · 42/1,179,956 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00279%
45/1,614,116 alleles · very rare
exomes 45/1,461,776 · genomes 0/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00356% | 28,094 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| East Asian | 0.00223% | 44,886 |
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.Pro125Ser
- Coding
- c.373C>T
- MANE Select
- NM_173852
- dbSNP
- rs908331937
- Type
- single nucleotide variant
- Location
- chr1:155169478 (GRCh38)
- Gene constraint
- LOEUF 1.04 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91 · 2 PDB
Similar variants
- 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
- KRTCAP2 c.-72A>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-pro125ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown