ZEB2 p.Ser424Arg
c.1270A>C · VCV3818893
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8912 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8912 | likely pathogenic |
|---|---|---|
| REVEL | 0.262 | benign-leaning |
| SaProt | LLR -8.62 | tolerated |
| ⇒ AlphaMissense calls this damaging; REVEL and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8 | GERP -0.48, phastCons 1 |
| Regional constraint | o/e 0.82 | unconstrained · MANE · 695 bp · p 0.0021 · regional, not allelic |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ZEB2
- Protein
- p.Ser424Arg
- Coding
- c.1270A>C
- MANE Select
- NM_014795
- Type
- single nucleotide variant
- Location
- chr2:144399917 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 48.91 · 1 PDB
Similar variants
- ZEB2 p.Arg343Ter Pathogenic ★★ same condition
- ZEB2 p.Arg921Ter Pathogenic ★★ same condition
- ZEB2 p.Gln275Ter Pathogenic ★★ same condition
- ZEB2 p.Leu965Ter Pathogenic ★★ same condition
- ZEB2 p.Tyr652Ter Pathogenic ★★ same condition
- ZEB2 p.Ala105Gly Uncertain significance ★★ ⚠ same condition
- ZEB2 p.Ala661Gly Uncertain significance ★★ ⚠ same condition
- ZEB2 p.Arg1180Gln Uncertain significance ★★ ⚠ 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-ser424arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown