CCDC33 p.Ala529Ser
c.1585G>T · rs368022401 · VCV2454877
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0132%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -1.7, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 99 kb · p 0.88 · regional, not allelic |
| Overall | ||
| CADD | 18.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0132%
European (non-Finnish) · 156/1,178,036 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0108%
Overall
0.0106%
171/1,609,906 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0132% | 7,552 |
| Remaining individualsnot grpmax-eligible | 0.0113% | 8,887 |
| African / African-American | 0.00535% | 18,701 |
| Admixed American | 0.00504% | 19,835 |
| South Asian | 0.00111% | 90,392 |
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.Ala529Ser
- Coding
- c.1585G>T
- MANE Select
- NM_025055
- dbSNP
- rs368022401
- Type
- single nucleotide variant
- Location
- chr15:74331020 (GRCh38)
- Gene constraint
- LOEUF 1.17 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.34
Similar variants
- CCDC33 p.Ala529Thr Uncertain significance ★ same residue
- 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
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-ala529ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown