CUL3 p.Thr8=
c.24G>C · rs139996986 · VCV2184988
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0179%, 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 2.1 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 13.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0179%
Middle Eastern · 1/5,576 alleles
Filtering AF
0.00863%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00801%
Overall
0.00802%
121/1,508,056 alleles · ultra-rare
exomes 114/1,359,360 · genomes 7/148,696 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0179% | 5,576 |
| European (non-Finnish) | 0.0102% | 9,801 |
| Remaining individualsnot grpmax-eligible | 0.00357% | 28,012 |
| African / African-American | 0.0029% | 34,514 |
| East Asian | 0.00268% | 37,264 |
| South Asian | 0.00117% | 85,790 |
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.Thr8=
- Coding
- c.24G>C
- MANE Select
- NM_003590
- dbSNP
- rs139996986
- Type
- single nucleotide variant
- Location
- chr2:224584986 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.68 · 31 PDB
- Residue 8
- the 'interaction with klhl18' region
Similar variants
- CUL3 p.Thr8Met 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-thr8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown