Is ZEB2 p.Pro514= (c.1542G>A) pathogenic?

ZEB2 p.Pro514= (c.1542G>A) is classified Conflicting classifications of pathogenicity in ZEB2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0117%, amr); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Pro514= (c.1542G>A)?

ZEB2 p.Pro514= (c.1542G>A) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Pro514= (c.1542G>A) in the general population?

ZEB2 p.Pro514= (c.1542G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

ZEB2 p.Pro514=

c.1542G>A · rs141674976 · VCV160318

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42	GERP -3.3, phastCons 0.19
Overall
CADD	10.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,004 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00632% 102/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,572
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.0072%	13,883
African / African-American	0.00267%	37,451
Finnishnot grpmax-eligible	0.00156%	64,032
South Asian	0.0011%	91,086

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.Pro514=
Coding: c.1542G>A
MANE Select: NM_014795
dbSNP: rs141674976
Type: single nucleotide variant
Location: chr2:144399645 (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.Pro514Leu 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-pro514 (accessed [today's date]).

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