Is ZEB2 p.Pro735Ser (c.2203C>T) pathogenic?

ZEB2 p.Pro735Ser (c.2203C>T) is classified Benign in ZEB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.1332); Low-frequency (popmax 1.97%, sas); Associated with Inborn genetic diseases.

What condition is associated with ZEB2 p.Pro735Ser (c.2203C>T)?

ZEB2 p.Pro735Ser (c.2203C>T) is associated with Inborn genetic diseases, Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Pro735Ser (c.2203C>T) in the general population?

ZEB2 p.Pro735Ser (c.2203C>T) is low-frequency (popmax 1.97%, sas) (gnomAD).

What do computational predictors say about ZEB2 p.Pro735Ser (c.2203C>T)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

ZEB2 p.Pro735Ser

c.2203C>T · rs144154908 · VCV95629

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.97%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 2,879 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	16.99	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

Grpmax group 1.97% South Asian · 1,795/91,078 alleles

Filtering AF 1.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.86%

Overall 0.118% 1,899/1,614,204 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.97%	51
Remaining individualsnot grpmax-eligible	0.133%	753
Middle Eastern	0.115%	866
African / African-American	0.00266%	37,524
East Asian	0.00223%	44,882
European (non-Finnish)	0.000932%	107,276

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.Pro735Ser
Coding: c.2203C>T
MANE Select: NM_014795
dbSNP: rs144154908
Type: single nucleotide variant
Location: chr2:144398984 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 48.91 · 1 PDB
Residue 735: the 'disordered' region

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.Pro735= Benign/Likely benign ★★ same residue
ZEB2 p.Pro735Arg Uncertain significance ★ ⚠ same residue
ZEB2 p.Pro735Leu Benign ★ 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

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-pro735ser (accessed [today's date]).

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