CUL3 p.Lys223=
c.669A>G · rs566891638 · VCV1958988
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.32 | GERP -0.88, phastCons 1 |
| Overall | ||
| CADD | 7.374 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,900 alleles
Filtering AF
0.000816%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000661%
Overall
0.00121%
19/1,570,156 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,900 |
| Admixed American | 0.00379% | 26,412 |
| European (non-Finnish) | 0.00138% | 72,521 |
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
- CUL3
- Protein
- p.Lys223=
- Coding
- c.669A>G
- MANE Select
- NM_003590
- dbSNP
- rs566891638
- Type
- single nucleotide variant
- Location
- chr2:224511568 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 223
- an α-helix
Similar variants
- CUL3 p.Lys223Thr Likely benign ★ same residue
- CUL3 c.1377+1G>A Pathogenic/Likely pathogenic ★★ same type
- CUL3 c.1377+4A>G Likely pathogenic ★★ same type
- CUL3 c.883+1G>A Pathogenic/Likely pathogenic ★★ same type
- CUL3 c.883+1G>T Pathogenic ★★ same type
- CUL3 p.Arg128Cys Pathogenic/Likely pathogenic ★★ same type
- CUL3 p.Arg148Ter Pathogenic ★★ same type
- CUL3 p.Arg247Ter 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/cul3-p-lys223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown