CUL9 p.Val459=
c.1377G>A · rs760357652 · VCV2656580
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.28%, 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 -0.45 | GERP -3.2 |
| Overall | ||
| CADD | 2.296 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.28%
Middle Eastern · 17/6,082 alleles
Filtering AF
0.178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.146%
Overall
0.0111%
179/1,613,892 alleles · rare
exomes 165/1,461,720 · genomes 14/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.28% | 358 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| Admixed American | 0.0333% | 3,000 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,165 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,859 |
| European (non-Finnish) | 0.0101% | 9,915 |
| East Asian | 0.00446% | 22,441 |
| African / African-American | 0.00267% | 37,455 |
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
- CUL9
- Protein
- p.Val459=
- Coding
- c.1377G>A
- MANE Select
- NM_015089
- dbSNP
- rs760357652
- Type
- single nucleotide variant
- Location
- chr6:43187085 (GRCh38)
- Gene constraint
- LOEUF 0.334 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.64 · 4 PDB
Similar variants
- CUL9 p.Glu617Lys Likely benign ★★ same type
- CUL9 c.1987+2T>C Uncertain significance ★ same type
- CUL9 p.Ala1004Val Uncertain significance ★ ⚠ same type
- CUL9 p.Ala1093Pro Uncertain significance ★ ⚠ same type
- CUL9 p.Ala1112Thr Uncertain significance ★ ⚠ same type
- CUL9 p.Ala111Thr Uncertain significance ★ ⚠ same type
- CUL9 p.Ala121Glu Uncertain significance ★ ⚠ same type
- CUL9 p.Ala131Val Uncertain significance ★ ⚠ 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/cul9-p-val459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown