CUX1 p.Ala54=
c.162G>A · VCV3341709
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0215%, 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 -3.7 | GERP -4.8 |
| Overall | ||
| CADD | 4.268 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0215%
Middle Eastern · 1/4,642 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00291%
47/1,612,460 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0215% | 4,642 |
| African / African-American | 0.0133% | 7,498 |
| South Asian | 0.0044% | 22,750 |
| Admixed American | 0.00333% | 30,008 |
| European (non-Finnish) | 0.00237% | 42,143 |
| East Asian | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,356 |
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.Ala54=
- Coding
- c.162G>A
- MANE Select
- NM_181552
- Type
- single nucleotide variant
- Location
- chr7:102028118 (GRCh38)
- Gene constraint
- LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 3 PDB
Similar variants
- CUX1 p.Ala54Gly Uncertain significance ★ ⚠ 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-ala54 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown