CUL3 p.Pro736fs
c.2207del · VCV4886463
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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 | escapes | premature termination codon in the last exon (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CUL3
- Protein
- p.Pro736fs
- Coding
- c.2207del
- MANE Select
- NM_003590
- Type
- Deletion
- Location
- chr2:224474345 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 736
- a UniProt-annotated variant site (in nedaus); the cullin neddylation domain
Similar variants
- CUL3 p.Pro736= Likely benign ★ same residue
- CUL3 p.Asn453fs Pathogenic ★★ same type
- CUL3 c.883+3_883+6del Uncertain significance ★★ same type
- CUL3 c.884-2del Likely pathogenic ★ same type
- CUL3 p.Ala226fs Pathogenic ★ same type
- CUL3 p.Ala40fs Pathogenic ★ same type
- CUL3 p.Arg158fs Pathogenic ★ same type
- CUL3 p.Arg180fs Likely 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-pro736fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown