ZEB2 p.Pro735=
c.2205T>C · rs149964599 · VCV137949
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.173%, afr)
Conditions
2
Inborn genetic diseases
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 -0.25 | GERP -3.3, phastCons 0.001 |
| Overall | ||
| CADD | 4.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.173%
African / African-American · 130/75,026 alleles
Filtering AF
0.149%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.14%
Overall
0.0144%
232/1,614,178 alleles · rare
exomes 148/1,461,872 · genomes 84/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.173% | 577 |
| Admixed American | 0.0466% | 2,144 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,315 |
| European (non-Finnish) | 0.00398% | 25,107 |
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.Pro735=
- Coding
- c.2205T>C
- MANE Select
- NM_014795
- dbSNP
- rs149964599
- Type
- single nucleotide variant
- Location
- chr2:144398982 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 48.91 · 1 PDB
- Residue 735
- the 'disordered' region
Similar variants
- ZEB2 p.Pro735Ser Benign ★★ same residue
- ZEB2 p.Pro735Arg Uncertain significance ★ ⚠ same residue
- ZEB2 p.Pro735Leu 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
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-pro735 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown