CWC27 p.Leu17=
c.49T>C · rs369814947 · VCV749565
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, eas)
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 0.28 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 6.914 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
East Asian · 18/43,158 alleles
Filtering AF
0.0269%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0223%
Overall
0.0043%
67/1,559,690 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0417% | 2,398 |
| Remaining individualsnot grpmax-eligible | 0.035% | 2,860 |
| African / African-American | 0.0194% | 5,163 |
| South Asian | 0.0146% | 6,829 |
| Admixed American | 0.00199% | 50,280 |
| European (non-Finnish) | 8.65e-05% | 1,155,600 |
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
- CWC27
- Protein
- p.Leu17=
- Coding
- c.49T>C
- MANE Select
- NM_005869
- dbSNP
- rs369814947
- Type
- single nucleotide variant
- Location
- chr5:64774697 (GRCh38)
- Gene constraint
- LOEUF 1.181 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.93 · 9 PDB
- Residue 17
- the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in rpska); a β-strand
Similar variants
- CWC27 c.1152+2T>A Likely pathogenic ★★ same type
- CWC27 c.397-1G>A Likely pathogenic ★★ same type
- CWC27 c.938+2T>C Likely pathogenic ★★ same type
- CWC27 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same type
- CWC27 p.Gln374Ter Pathogenic/Likely pathogenic ★★ same type
- CWC27 p.Glu165= Pathogenic ★★ same type
- CWC27 p.Tyr367Ter Pathogenic/Likely pathogenic ★★ same type
- CWC27 c.1042+5G>A 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/cwc27-p-leu17 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown