CCDC33 p.Arg436Trp
c.1306C>T · rs756387713 · VCV3139110
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00885%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.222 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 99 kb · p 0.88 · regional, not allelic |
| Overall | ||
| CADD | 27.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00885%
South Asian · 8/90,360 alleles
Filtering AF
0.0044%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00314%
Overall
0.00143%
23/1,606,932 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00885% | 11,295 |
| Admixed American | 0.00337% | 29,704 |
| African / African-American | 0.00268% | 37,333 |
| East Asian | 0.00224% | 44,678 |
| European (non-Finnish) | 0.00085% | 117,589 |
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.Arg436Trp
- Coding
- c.1306C>T
- MANE Select
- NM_025055
- dbSNP
- rs756387713
- Type
- single nucleotide variant
- Location
- chr15:74330204 (GRCh38)
- Gene constraint
- LOEUF 1.17 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.34
Similar variants
- CCDC33 p.Arg436Gln 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-arg436trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown