Is ZEB2 p.Ser106Phe (c.317C>T) pathogenic?

ZEB2 p.Ser106Phe (c.317C>T) is classified Uncertain significance in ZEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely benign (0.2022); Very rare (popmax 8.48e-05%, nfe); Associated with Mowat-Wilson syndrome.

What condition is associated with ZEB2 p.Ser106Phe (c.317C>T)?

ZEB2 p.Ser106Phe (c.317C>T) is associated with Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Ser106Phe (c.317C>T) in the general population?

ZEB2 p.Ser106Phe (c.317C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ZEB2 p.Ser106Phe (c.317C>T)?

AlphaMissense predicts likely benign (score 0.2022) — an in-silico prediction, not a clinical call.

ZEB2 p.Ser106Phe

c.317C>T · rs2549120597 · VCV2698652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Mowat-Wilson syndrome

Computational evidence

Protein change
AlphaMissense	0.2022	likely benign
REVEL	0.7	pathogenic-leaning
SaProt	LLR -7.68	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 112 kb · p 0.0024 · regional, not allelic
Overall
CADD	27.3	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 8.48e-05% European (non-Finnish) · 1/1,179,814 alleles

Overall 6.84e-05% 1/1,461,564 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.Ser106Phe
Coding: c.317C>T
MANE Select: NM_014795
dbSNP: rs2549120597
Type: single nucleotide variant
Location: chr2:144429783 (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.Ser106= Likely 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-ser106phe (accessed [today's date]).

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