CWC27 c.252+4del
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00883%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 5.3, phastCons 1 |
| Non-coding constraint | Z 2.19 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 14.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00883%
African / African-American · 6/67,924 alleles
Filtering AF
0.00377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00258%
Overall
0.000603%
8/1,326,002 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00883% | 11,321 |
| Finnishnot grpmax-eligible | 0.00165% | 60,594 |
| European (non-Finnish) | 0.000105% | 950,480 |
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
- Coding
- c.252+4del
- MANE Select
- NM_005869
- dbSNP
- rs1200215248
- Type
- Deletion
- Location
- chr5:64782036 (GRCh38)
- Gene constraint
- LOEUF 1.181 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.93 · 9 PDB
Similar variants
- CWC27 c.249_252+22del Likely pathogenic ★★ same type
- CWC27 p.Ala356fs Pathogenic ★★ same type
- CWC27 p.Asn109fs Pathogenic/Likely pathogenic ★★ same type
- CWC27 p.Gly253fs Pathogenic/Likely pathogenic ★★ same type
- CWC27 p.Lys334_Val335insTer Pathogenic/Likely pathogenic ★★ same type
- CWC27 p.Ser222fs Pathogenic ★★ same type
- CWC27 p.Glu470fs Uncertain significance ★★ same type
- CWC27 c.1257-7del Likely 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/cwc27-c-252-plus-4del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown