Is ZEB2 p.Ser358fs (c.1072dup) pathogenic?

ZEB2 p.Ser358fs (c.1072dup) is classified Uncertain significance in ZEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Ser358fs (c.1072dup)?

ZEB2 p.Ser358fs (c.1072dup) is associated with Mowat-Wilson syndrome (ClinVar).

ZEB2 p.Ser358fs

c.1072dup · VCV4278107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ZEB2
Protein: p.Ser358fs
Coding: c.1072dup
MANE Select: NM_014795
Type: Duplication
Location: chr2:144400114 (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

ZEB2 p.Ser358Thr Uncertain significance ★ ⚠ same residue
ZEB2 c.73+2dup Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.Asp568_Asp569insTer Pathogenic ★★ same condition
ZEB2 p.Leu786fs Pathogenic ★★ same condition
ZEB2 p.Met476fs Pathogenic ★★ same condition
ZEB2 p.Thr752fs Pathogenic ★★ same condition
ZEB2 p.Tyr293fs Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.Ala208fs 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-ser358fs (accessed [today's date]).

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