Is ZEB2 p.His73= (c.219C>T) pathogenic?

ZEB2 p.His73= (c.219C>T) is classified Conflicting classifications of pathogenicity in ZEB2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0155%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ZEB2 p.His73= (c.219C>T)?

ZEB2 p.His73= (c.219C>T) is associated with Inborn genetic diseases, Mowat-Wilson syndrome (ClinVar).

How common is ZEB2 p.His73= (c.219C>T) in the general population?

ZEB2 p.His73= (c.219C>T) is ultra-rare (popmax 0.0155%, nfe) (gnomAD).

ZEB2 p.His73=

c.219C>T · rs778851716 · VCV196468

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.033	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 1.1, phastCons 1
Overall
CADD	11.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0155% European (non-Finnish) · 183/1,179,868 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0118% 191/1,613,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0155%	6,447
Remaining individualsnot grpmax-eligible	0.0048%	20,823
African / African-American	0.00401%	24,951
Admixed American	0.00167%	59,918
Finnishnot grpmax-eligible	0.00156%	64,014

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.His73=
Coding: c.219C>T
MANE Select: NM_014795
dbSNP: rs778851716
Type: single nucleotide variant
Location: chr2:144429881 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 48.91 · 1 PDB
Residue 73: 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 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-his73 (accessed [today's date]).

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