ZEB2 p.Pro66=
c.198C>T · VCV4739582
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00501%, amr)
Conditions
1
Mowat-Wilson syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.688 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP -0.61, phastCons 1 |
| Overall | ||
| CADD | 11.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00501%
Admixed American · 3/59,910 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00031%
5/1,613,654 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00501% | 19,970 |
| African / African-American | 0.00267% | 37,417 |
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
- ZEB2
- Protein
- p.Pro66=
- Coding
- c.198C>T
- MANE Select
- NM_014795
- Type
- single nucleotide variant
- Location
- chr2:144429902 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 48.91 · 1 PDB
- Residue 66
- the 'disordered' region
Similar variants
- ZEB2 p.Pro66Leu Uncertain significance ★ ⚠ same residue
- ZEB2 p.Pro66Thr Likely benign ★ same residue
- ZEB2 c.2886+1G>A Pathogenic ★★ same condition
- ZEB2 c.73+1G>A Pathogenic ★★ same condition
- ZEB2 c.73+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ZEB2 c.808-2A>G Pathogenic ★★ same condition
- ZEB2 p.Arg1016Ter Pathogenic/Likely pathogenic ★★ same condition
- ZEB2 p.Arg302Ter Pathogenic/Likely pathogenic ★★ same condition
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/zeb2-p-pro66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown