CUX2 p.Pro1254=
c.3762A>C · rs1592994912 · VCV736188
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.129%, eas)
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 |
|---|---|---|
| Pangolin | Δ0.21 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.35 | GERP -3.4 |
| Overall | ||
| CADD | 1.596 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
East Asian · 29/22,566 alleles
Filtering AF
0.0919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0867%
Overall
0.0754%
566/751,032 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.129% | 778 |
| Remaining individualsnot grpmax-eligible | 0.118% | 844 |
| European (non-Finnish) | 0.0972% | 1,029 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0927% | 1,079 |
| Middle Eastern | 0.0531% | 1,882 |
| African / African-American | 0.0342% | 2,923 |
| Admixed American | 0.0247% | 4,051 |
| Finnishnot grpmax-eligible | 0.018% | 5,562 |
| South Asian | 0.0107% | 9,388 |
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.Pro1254=
- Coding
- c.3762A>C
- MANE Select
- NM_015267
- dbSNP
- rs1592994912
- Type
- single nucleotide variant
- Location
- chr12:111347626 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 3 PDB
- Residue 1254
- 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-pro1254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown