CWC27 p.Ala81=
c.243G>A · rs753031106 · VCV1082716
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00543%, nfe)
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 -1.3 | GERP 0.41 |
| Overall | ||
| CADD | 10.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00543%
European (non-Finnish) · 59/1,086,282 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00392%
Overall
0.00423%
63/1,490,624 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00543% | 18,412 |
| African / African-American | 0.00418% | 23,909 |
| Remaining individualsnot grpmax-eligible | 0.00173% | 57,768 |
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.Ala81=
- Coding
- c.243G>A
- MANE Select
- NM_005869
- dbSNP
- rs753031106
- Type
- single nucleotide variant
- Location
- chr5:64782024 (GRCh38)
- Gene constraint
- LOEUF 1.181 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.93 · 9 PDB
- Residue 81
- the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in rpska)
Similar variants
- CWC27 p.Ala81Val Uncertain significance ★ ⚠ same residue
- 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
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-ala81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown