CUX1 p.Ser747=
c.2241C>T · VCV4534753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.03%, amr)
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 -0.089 | GERP -3.2 |
| Overall | ||
| CADD | 4.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.03%
Admixed American · 18/60,022 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00118%
19/1,614,148 alleles · ultra-rare
exomes 19/1,461,882 · genomes 0/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.03% | 3,335 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
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
- CUX1
- Protein
- p.Ser747=
- Coding
- c.2241C>T
- MANE Select
- NM_181552
- Type
- single nucleotide variant
- Location
- chr7:102201538 (GRCh38)
- Gene constraint
- LOEUF 0.277 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 3 PDB
- Residue 747
- a functional site (cleavage; by ctsl)
Similar variants
- CUX1 p.Ser747Cys Uncertain significance ★ ⚠ same residue
- CUX1 c.1451-2A>G Likely pathogenic ★★ same type
- CUX1 c.1681-1G>A Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Arg661Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Gln862Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Glu866Ter Pathogenic/Likely pathogenic ★★ same type
- CUX1 p.Trp1188Ter Pathogenic ★★ same type
- CUX1 p.Ala1433Val 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/cux1-p-ser747 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown