CUX2 p.Ala543=
c.1629G>A · rs200518721 · VCV2643297
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.306%, 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 -0.24 | GERP -2.2 |
| Overall | ||
| CADD | 0.366 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.306%
African / African-American · 230/75,058 alleles
Filtering AF
0.274%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.261%
Overall
0.0218%
351/1,610,806 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.306% | 326 |
| Admixed American | 0.035% | 2,856 |
| Middle Eastern | 0.0343% | 2,915 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,925 |
| European (non-Finnish) | 0.00721% | 13,868 |
| South Asian | 0.0044% | 22,750 |
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
- CUX2
- Protein
- p.Ala543=
- Coding
- c.1629G>A
- MANE Select
- NM_015267
- dbSNP
- rs200518721
- Type
- single nucleotide variant
- Location
- chr12:111310411 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 3 PDB
- Residue 543
- the 'disordered' region
Similar variants
- CUX2 p.Glu590Lys Pathogenic/Likely pathogenic ★★ same type
- CUX2 p.Ala302Ser Uncertain significance ★★ ⚠ same type
- CUX2 p.Ala336Thr Uncertain significance ★★ ⚠ same type
- CUX2 p.Ala544Val Uncertain significance ★★ ⚠ same type
- CUX2 p.Arg312Gln Uncertain significance ★★ ⚠ same type
- CUX2 p.Arg599Ser Uncertain significance ★★ ⚠ same type
- CUX2 p.Arg701His Uncertain significance ★★ ⚠ same type
- CUX2 p.Arg903His 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/cux2-p-ala543 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown