Is TJP2 p.Ser266Arg (c.798C>G) pathogenic?

TJP2 p.Ser266Arg (c.798C>G) is classified Uncertain significance in TJP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.2945); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Ser266Arg (c.798C>G)?

TJP2 p.Ser266Arg (c.798C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Ser266Arg (c.798C>G) in the general population?

TJP2 p.Ser266Arg (c.798C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TJP2 p.Ser266Arg (c.798C>G)?

AlphaMissense predicts likely benign (score 0.2945) — an in-silico prediction, not a clinical call.

TJP2 p.Ser266Arg

c.798C>G · VCV3969097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2945	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	18.2	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

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: TJP2
Protein: p.Ser266Arg
Coding: c.798C>G
MANE Select: NM_004817
Type: single nucleotide variant
Location: chr9:69221342 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.92 · 2 PDB
Residue 266: a modified residue (phosphoserine); the 'disordered' region

Full TJP2 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

Similar variants

TJP2 p.Arg591Ter Pathogenic ★★ same condition
TJP2 p.Ala544Val Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1047Pro Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1167Cys Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1167His Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1167Leu Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1176His Uncertain significance ★★ ⚠ same condition
TJP2 p.Arg1184Gln Uncertain significance ★★ ⚠ 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/tjp2-p-ser266arg (accessed [today's date]).

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