CUL3 p.Pro738=
c.2214A>G · rs752027394 · VCV2414341
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 15.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,966 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00682%
Overall
0.000744%
12/1,613,788 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,997 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 8.48e-05% | 1,179,885 |
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.Pro738=
- Coding
- c.2214A>G
- MANE Select
- NM_003590
- dbSNP
- rs752027394
- Type
- single nucleotide variant
- Location
- chr2:224474338 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 738
- a UniProt-annotated variant site (in nedaus); the cullin neddylation domain
Similar variants
- 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
- CUL3 p.Arg438Gly 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-pro738 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown