CUX2 p.Asp648=
c.1944C>T · rs199957017 · VCV2643298
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, sas)
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 -10 | GERP -3.4 |
| Overall | ||
| CADD | 0.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
South Asian · 969/90,916 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.988%
Overall
0.137%
2,205/1,612,482 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.07% | 94 |
| Middle Eastern | 0.446% | 224 |
| Ashkenazi Jewishnot grpmax-eligible | 0.335% | 299 |
| Remaining individualsnot grpmax-eligible | 0.168% | 595 |
| Admixed American | 0.085% | 1,176 |
| European (non-Finnish) | 0.0799% | 1,251 |
| African / African-American | 0.0147% | 6,820 |
| East Asian | 0.00223% | 44,824 |
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.Asp648=
- Coding
- c.1944C>T
- MANE Select
- NM_015267
- dbSNP
- rs199957017
- Type
- single nucleotide variant
- Location
- chr12:111312143 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 3 PDB
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-asp648 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown