Is ZEB2 p.Ser707Phe (c.2120C>T) pathogenic?

ZEB2 p.Ser707Phe (c.2120C>T) is classified Likely benign in ZEB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1517); Very rare (popmax 0.000424%, nfe); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Ser707Phe (c.2120C>T)?

ZEB2 p.Ser707Phe (c.2120C>T) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Ser707Phe (c.2120C>T) in the general population?

ZEB2 p.Ser707Phe (c.2120C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ZEB2 p.Ser707Phe (c.2120C>T)?

AlphaMissense predicts likely benign (score 0.1517) — an in-silico prediction, not a clinical call.

ZEB2 p.Ser707Phe

c.2120C>T · rs1174325176 · VCV534645

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
AlphaMissense	0.1517	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -9.70	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 2,879 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	27.0	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 0.000424% European (non-Finnish) · 5/1,180,024 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,868 alleles · very rare

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.Ser707Phe
Coding: c.2120C>T
MANE Select: NM_014795
dbSNP: rs1174325176
Type: single nucleotide variant
Location: chr2:144399067 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 48.91 · 1 PDB
Residue 707: the 'disordered' region

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.Ser707Thr 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
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-ser707phe (accessed [today's date]).

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