Is ZEB2 p.Pro882Ser (c.2644C>T) pathogenic?

ZEB2 p.Pro882Ser (c.2644C>T) is classified Uncertain significance in ZEB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.117); Absent from gnomAD v4.1; Associated with ZEB2-related disorder.

What condition is associated with ZEB2 p.Pro882Ser (c.2644C>T)?

ZEB2 p.Pro882Ser (c.2644C>T) is associated with ZEB2-related disorder (ClinVar).

How common is ZEB2 p.Pro882Ser (c.2644C>T) in the general population?

ZEB2 p.Pro882Ser (c.2644C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ZEB2 p.Pro882Ser (c.2644C>T)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

ZEB2 p.Pro882Ser

c.2644C>T · rs2549105794 · VCV2629688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ZEB2-related disorder

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.38	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 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 2,879 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ZEB2
Protein: p.Pro882Ser
Coding: c.2644C>T
MANE Select: NM_014795
dbSNP: rs2549105794
Type: single nucleotide variant
Location: chr2:144398543 (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

ZEB2-related disorder

Similar variants

ZEB2 p.Pro882= Likely benign ★★ same residue
ZEB2 p.Arg1016Ter Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.Arg302Ter Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.Arg695Ter Pathogenic ★★ same condition
ZEB2 p.His1049Pro Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.His300Tyr Pathogenic/Likely pathogenic ★★ same condition
ZEB2 p.Tyr489Ter Pathogenic ★★ same condition
ZEB2 p.Gln550Ter 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-pro882ser (accessed [today's date]).

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