CUX2 p.Thr992=
c.2976A>C · rs2499909623 · VCV3025551
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.37 | acceptor loss, 6 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -3.4 |
| Overall | ||
| CADD | 3.841 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
African / African-American · 1/73,476 alleles
Filtering AF
6.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000277%
4/1,444,222 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00136% | 73,476 |
| European (non-Finnish) | 0.000257% | 388,445 |
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.Thr992=
- Coding
- c.2976A>C
- MANE Select
- NM_015267
- dbSNP
- rs2499909623
- Type
- single nucleotide variant
- Location
- chr12:111334490 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 3 PDB
- Residue 992
- the 'disordered' region
Similar variants
- CUX2 p.Thr992Ile 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-thr992 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown