Is ZEB2 p.Val503Phe (c.1507G>T) pathogenic?

ZEB2 p.Val503Phe (c.1507G>T) is classified Uncertain significance in ZEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-02). AlphaMissense: likely benign (0.0893); Very rare (popmax 0.00167%, amr); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Val503Phe (c.1507G>T)?

ZEB2 p.Val503Phe (c.1507G>T) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Val503Phe (c.1507G>T) in the general population?

ZEB2 p.Val503Phe (c.1507G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ZEB2 p.Val503Phe (c.1507G>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

ZEB2 p.Val503Phe

c.1507G>T · rs1203180157 · VCV2116570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 695 bp · p 0.0021 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
European (non-Finnish)	0.000254%	393,345

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.Val503Phe
Coding: c.1507G>T
MANE Select: NM_014795
dbSNP: rs1203180157
Type: single nucleotide variant
Location: chr2:144399680 (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 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-val503phe (accessed [today's date]).

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