ZEB2 p.Ser75=
c.225C>T · rs754754722 · VCV381140
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, nfe)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.06 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 13.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
European (non-Finnish) · 197/1,179,870 alleles
Filtering AF
0.0148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.014%
Overall
0.0125%
201/1,613,636 alleles · ultra-rare
exomes 197/1,461,644 · genomes 4/151,992 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0167% | 5,989 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| African / African-American | 0.00134% | 74,834 |
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.Ser75=
- Coding
- c.225C>T
- MANE Select
- NM_014795
- dbSNP
- rs754754722
- Type
- single nucleotide variant
- Location
- chr2:144429875 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 48.91 · 1 PDB
- Residue 75
- the 'disordered' region
Similar variants
- ZEB2 p.Ser75Asn 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
- ZEB2 p.Arg343Ter 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-ser75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown