CUX2 p.Pro819=
c.2457C>A · rs201135503 · VCV2643302
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 2.6 | GERP 0.038, phastCons 1 |
| Overall | ||
| CADD | 10.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,054 alleles
Filtering AF
0.0201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0193%
Overall
0.0175%
278/1,591,216 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,027 |
| European (non-Finnish) | 0.0224% | 4,463 |
| Admixed American | 0.0117% | 8,553 |
| Remaining individualsnot grpmax-eligible | 0.00645% | 15,506 |
| African / African-American | 0.00134% | 74,588 |
| South Asian | 0.0011% | 90,832 |
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.Pro819=
- Coding
- c.2457C>A
- MANE Select
- NM_015267
- dbSNP
- rs201135503
- Type
- single nucleotide variant
- Location
- chr12:111320466 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 3 PDB
- Residue 819
- the 'disordered' region
Similar variants
- CUX2 p.Pro819Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro819 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown