Is ZEB2 p.Ile102Phe (c.304A>T) pathogenic?

ZEB2 p.Ile102Phe (c.304A>T) is classified Benign/Likely benign in ZEB2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ZEB2 p.Ile102Phe (c.304A>T)?

ZEB2 p.Ile102Phe (c.304A>T) is associated with Inborn genetic diseases, Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.Ile102Phe (c.304A>T) in the general population?

ZEB2 p.Ile102Phe (c.304A>T) is ultra-rare (popmax 0.0424%, nfe) (gnomAD).

What do computational predictors say about ZEB2 p.Ile102Phe (c.304A>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

ZEB2 p.Ile102Phe

c.304A>T · rs201109457 · VCV181724

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -7.02	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 2	GERP 0.35, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 112 kb · p 0.0024 · regional, not allelic
Overall
CADD	17.48	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 0.0424% European (non-Finnish) · 500/1,179,830 alleles

Filtering AF 0.0392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0381%

Overall 0.033% 533/1,613,696 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0424%	2,360
Remaining individualsnot grpmax-eligible	0.0224%	4,462
Finnishnot grpmax-eligible	0.0219%	4,573
African / African-American	0.00401%	24,958
Admixed American	0.00334%	29,974

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.Ile102Phe
Coding: c.304A>T
MANE Select: NM_014795
dbSNP: rs201109457
Type: single nucleotide variant
Location: chr2:144429796 (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 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
ZEB2 p.Arg695Ter 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-ile102phe (accessed [today's date]).

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