ZEB1 p.Pro892=
c.2676G>A · rs751487849 · VCV728757
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 9.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,074 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00229%
37/1,613,634 alleles · ultra-rare
exomes 33/1,461,682 · genomes 4/151,952 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,107 |
| Admixed American | 0.00834% | 11,992 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| African / African-American | 0.00267% | 37,422 |
| East Asian | 0.00223% | 44,816 |
| European (non-Finnish) | 0.00119% | 84,278 |
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
- ZEB1
- Protein
- p.Pro892=
- Coding
- c.2676G>A
- MANE Select
- NM_001174096
- dbSNP
- rs751487849
- Type
- single nucleotide variant
- Location
- chr10:31524004 (GRCh38)
- Gene constraint
- LOEUF 0.339 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 48.64 · 1 PDB
- Residue 892
- the 'disordered' region
Similar variants
- ZEB1 p.Pro892Leu Uncertain significance ★ ⚠ same residue
- ZEB1 p.Arg326Ter Pathogenic ★★ same type
- ZEB1 p.Glu120Lys Uncertain significance ★★ ⚠ same type
- ZEB1 p.Glu481Gln Uncertain significance ★★ ⚠ same type
- ZEB1 p.Glu74Lys Uncertain significance ★★ ⚠ same type
- ZEB1 p.Ile333Thr Uncertain significance ★★ ⚠ same type
- ZEB1 c.688-15G>A Benign ★★ same type
- ZEB1 p.Ala420= Benign ★★ 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/zeb1-p-pro892 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown