CUX1 p.Ala1083=
c.3249G>A · rs189647354 · VCV750502
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.03%, amr)
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 -4.7 | GERP -5.3 |
| Overall | ||
| CADD | 0.479 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.03%
Admixed American · 18/59,996 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00235%
38/1,614,042 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.03% | 3,333 |
| African / African-American | 0.004% | 25,011 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| European (non-Finnish) | 0.00127% | 78,668 |
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
- CUX1
- Protein
- p.Ala1083=
- Coding
- c.3249G>A
- MANE Select
- NM_181552
- dbSNP
- rs189647354
- Type
- single nucleotide variant
- Location
- chr7:102227485 (GRCh38)
- Gene constraint
- LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 3 PDB
- Residue 1083
- the 'disordered' region; a UniProt-annotated variant site (in neddms)
Similar variants
- CUX1 p.Ala1083Val Likely benign ★ same residue
- CUX1 c.1451-2A>G Likely pathogenic ★★ same type
- CUX1 c.1681-1G>A Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Arg661Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Gln862Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Glu866Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Trp1188Ter Pathogenic ★★ same type
- CUX1 p.Ala1433Val 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/cux1-p-ala1083 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown