CCDC33 p.Val355Met
c.1063G>A · rs373900085 · VCV2366732
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0423%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.079 | 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 1.00 | unconstrained · MANE · 99 kb · p 0.88 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0423%
East Asian · 19/44,892 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.023%
Overall
0.00242%
39/1,614,098 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0423% | 2,363 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,251 |
| South Asian | 0.00439% | 22,763 |
| African / African-American | 0.00266% | 37,527 |
| Admixed American | 0.00167% | 60,022 |
| European (non-Finnish) | 0.000254% | 393,328 |
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
- CCDC33
- Protein
- p.Val355Met
- Coding
- c.1063G>A
- MANE Select
- NM_025055
- dbSNP
- rs373900085
- Type
- single nucleotide variant
- Location
- chr15:74281817 (GRCh38)
- Gene constraint
- LOEUF 1.17 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.34
Similar variants
- CCDC33 p.Pro610Leu Likely benign ★★ same type
- STRA6 c.96+1744C>G Benign ★★ same type
- STRA6 c.-15-751T>G Benign ★★ same type
- STRA6 c.-16+1061C>G Likely benign ★★ same type
- STRA6 c.-16+1161G>A Benign ★★ same type
- STRA6 c.-16+794G>C Benign ★★ same type
- STRA6 c.-5200G>A Benign ★★ same type
- STRA6 p.Trp15Ter 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/ccdc33-p-val355met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown