CUL3 p.Ser221fs
c.659_662dup · VCV4853697
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
CUL3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 16 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP 1.2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CUL3
- Protein
- p.Ser221fs
- Coding
- c.659_662dup
- MANE Select
- NM_003590
- Type
- Duplication
- Location
- chr2:224511574 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 221
- an α-helix
Disease context
CUL3-related disorder
Similar variants
- CUL3 p.Val65fs Likely pathogenic ★ same condition
- CUL3 c.1377+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CUL3 c.540_541del Pathogenic/Likely pathogenic ★★ same condition
- CUL3 p.Arg438Gly Pathogenic ★★ same condition
- CUL3 p.Gln368fs Pathogenic/Likely pathogenic ★★ same condition
- CUL3 c.1207-12T>A Likely pathogenic ★ same condition
- CUL3 p.Asp413Gly Likely pathogenic ★ same condition
- CUL3 p.Cys187Tyr Likely pathogenic ★ same condition
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-ser221fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown