Is ZEB2 p.Arg15Ser (c.43C>A) pathogenic?

ZEB2 p.Arg15Ser (c.43C>A) is classified Uncertain significance in ZEB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-08). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Arg15Ser (c.43C>A)?

ZEB2 p.Arg15Ser (c.43C>A) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Arg15Ser (c.43C>A) in the general population?

ZEB2 p.Arg15Ser (c.43C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZEB2 p.Arg15Ser (c.43C>A)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

ZEB2 p.Arg15Ser

c.43C>A · rs1705171747 · VCV2112417

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic · top 7% in ZEB2
REVEL	0.542	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 112 kb · p 0.0024 · regional, not allelic
Overall
CADD	28.9	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.Arg15Ser
Coding: c.43C>A
MANE Select: NM_014795
dbSNP: rs1705171747
Type: single nucleotide variant
Location: chr2:144517308 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 48.91 · 1 PDB
Residue 15: the 'disordered' region

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.Arg15Leu Uncertain significance ★ ⚠ same residue
ZEB2 p.Arg15Gly 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

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-arg15ser (accessed [today's date]).

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