Is ZEB2 p.Pro922= (c.2766A>T) pathogenic?

ZEB2 p.Pro922= (c.2766A>T) is classified Conflicting classifications of pathogenicity in ZEB2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-27). Ultra-rare (popmax 0.045%, amr); Associated with Inborn genetic diseases.

What condition is associated with ZEB2 p.Pro922= (c.2766A>T)?

ZEB2 p.Pro922= (c.2766A>T) is associated with Inborn genetic diseases, Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Pro922= (c.2766A>T) in the general population?

ZEB2 p.Pro922= (c.2766A>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

ZEB2 p.Pro922=

c.2766A>T · rs185223937 · VCV137952

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 0.045%, amr)

Conditions

Inborn genetic diseases

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 0.95	GERP 0.77, phastCons 1
Overall
CADD	7.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/60,026 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0026% 42/1,614,142 alleles · ultra-rare exomes 14/1,461,818 · genomes 28/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0192%	5,209
African / African-American	0.00266%	37,525
European (non-Finnish)	8.47e-05%	1,179,984

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.Pro922=
Coding: c.2766A>T
MANE Select: NM_014795
dbSNP: rs185223937
Type: single nucleotide variant
Location: chr2:144398421 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Mowat-Wilson syndrome

Similar variants

ZEB2 p.Pro922Ala Uncertain significance ★ ⚠ same residue
ZEB2 p.Pro922Ser 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-pro922 (accessed [today's date]).

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