CUL3 p.Asp697=
c.2091C>T · VCV4960199
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 -1.9 | GERP -3.4 |
| Overall | ||
| CADD | 8.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,860 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000682%
11/1,613,446 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,430 |
| European (non-Finnish) | 0.000763% | 131,083 |
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.Asp697=
- Coding
- c.2091C>T
- MANE Select
- NM_003590
- Type
- single nucleotide variant
- Location
- chr2:224478284 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 697
- a UniProt-annotated variant site (in nedaus); the 'disordered' region
Similar variants
- CUL3 p.Asp697Asn 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-asp697 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown