Is ZEB2 p.Arg253= (c.759C>T) pathogenic?

ZEB2 p.Arg253= (c.759C>T) is classified Benign/Likely benign in ZEB2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.0501%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ZEB2 p.Arg253= (c.759C>T)?

ZEB2 p.Arg253= (c.759C>T) is associated with Inborn genetic diseases, Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Arg253= (c.759C>T) in the general population?

ZEB2 p.Arg253= (c.759C>T) is ultra-rare (popmax 0.0501%, nfe) (gnomAD).

ZEB2 p.Arg253=

c.759C>T · rs150853991 · VCV137943

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.116	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP -0.036, phastCons 1
Overall
CADD	10.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0501% European (non-Finnish) · 591/1,180,024 alleles

Filtering AF 0.0467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0454%

Overall 0.0386% 623/1,614,156 alleles · ultra-rare exomes 575/1,461,882 · genomes 48/152,274 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0501%	1,997
Remaining individualsnot grpmax-eligible	0.024%	4,167
Middle Eastern	0.0165%	6,062
African / African-American	0.0107%	9,379
Admixed American	0.00833%	12,005
Finnishnot grpmax-eligible	0.00469%	21,343

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.Arg253=
Coding: c.759C>T
MANE Select: NM_014795
dbSNP: rs150853991
Type: single nucleotide variant
Location: chr2:144403964 (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.Arg253Ser Conflicting classifications of pathogenicity ★ ⚠ 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-arg253 (accessed [today's date]).

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