Is ZEB2 p.Pro430Ser (c.1288C>T) pathogenic?

ZEB2 p.Pro430Ser (c.1288C>T) is classified Conflicting classifications of pathogenicity in ZEB2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-24). AlphaMissense: likely benign (0.0581); Very rare (popmax 0.00333%, amr); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Pro430Ser (c.1288C>T)?

ZEB2 p.Pro430Ser (c.1288C>T) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Pro430Ser (c.1288C>T) in the general population?

ZEB2 p.Pro430Ser (c.1288C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ZEB2 p.Pro430Ser (c.1288C>T)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

ZEB2 p.Pro430Ser

c.1288C>T · rs753804606 · VCV388030

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 695 bp · p 0.0021 · regional, not allelic
Overall
CADD	17.26	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

Grpmax group 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,461,870 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,010
African / African-American	0.00266%	37,526

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.Pro430Ser
Coding: c.1288C>T
MANE Select: NM_014795
dbSNP: rs753804606
Type: single nucleotide variant
Location: chr2:144399899 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 48.91 · 1 PDB

Full ZEB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Mowat-Wilson syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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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
ZEB2 p.Arg695Ter 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-pro430ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown