CUL3 p.Asp696=
c.2088C>T · rs374533358 · VCV2195670
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.116%, 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 -2.3 | GERP -4.2 |
| Overall | ||
| CADD | 5.276 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
Middle Eastern · 7/6,052 alleles
Filtering AF
0.0542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0384%
Overall
0.00669%
108/1,613,522 alleles · rare
exomes 77/1,461,416 · genomes 31/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.116% | 865 |
| Admixed American | 0.0217% | 4,614 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,247 |
| African / African-American | 0.008% | 12,495 |
| European (non-Finnish) | 0.00585% | 17,098 |
| East Asian | 0.00446% | 22,424 |
| South Asian | 0.0011% | 91,006 |
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.Asp696=
- Coding
- c.2088C>T
- MANE Select
- NM_003590
- dbSNP
- rs374533358
- Type
- single nucleotide variant
- Location
- chr2:224478287 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 696
- a UniProt-annotated variant site (in nedaus); the 'disordered' region
Similar variants
- CUL3 p.Asp696Asn Uncertain significance ★ ⚠ 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-asp696 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown