CCDC33 p.Arg625Trp
c.1873C>T · rs184774328 · VCV2470878
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.173%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.229 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.21 | GERP 1.5, phastCons 0.005 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 99 kb · p 0.88 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.173%
African / African-American · 130/75,042 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.14%
Overall
0.0096%
155/1,614,186 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.173% | 577 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,251 |
| Admixed American | 0.00666% | 15,007 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000763% | 131,115 |
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.Arg625Trp
- Coding
- c.1873C>T
- MANE Select
- NM_025055
- dbSNP
- rs184774328
- Type
- single nucleotide variant
- Location
- chr15:74332780 (GRCh38)
- Gene constraint
- LOEUF 1.17 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.34
- Residue 625
- the 'disordered' region
Similar variants
- CCDC33 p.Arg625Gln 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-arg625trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown