Is ZEB2 p.Ser242= (c.726C>T) pathogenic?

ZEB2 p.Ser242= (c.726C>T) is classified Likely benign in ZEB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-24). Ultra-rare (popmax 0.0164%, mid); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Ser242= (c.726C>T)?

ZEB2 p.Ser242= (c.726C>T) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Ser242= (c.726C>T) in the general population?

ZEB2 p.Ser242= (c.726C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ZEB2 p.Ser242=

c.726C>T · rs929943753 · VCV1218174

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.95, phastCons 1
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000558% 9/1,614,036 alleles · ultra-rare exomes 7/1,461,888 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0022%	45,540
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000424%	236,009

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.Ser242=
Coding: c.726C>T
MANE Select: NM_014795
dbSNP: rs929943753
Type: single nucleotide variant
Location: chr2:144403997 (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.Ser242Phe Uncertain significance ★★ ⚠ 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-ser242 (accessed [today's date]).

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