Is TJP2 p.Arg183Pro (c.548G>C) pathogenic?

TJP2 p.Arg183Pro (c.548G>C) is classified Uncertain significance in TJP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely benign (0.1115); Very rare (popmax 0.00231%, eas); Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Arg183Pro (c.548G>C)?

TJP2 p.Arg183Pro (c.548G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Arg183Pro (c.548G>C) in the general population?

TJP2 p.Arg183Pro (c.548G>C) is very rare (popmax 0.00231%, eas) (gnomAD).

What do computational predictors say about TJP2 p.Arg183Pro (c.548G>C)?

AlphaMissense predicts likely benign (score 0.1115) — an in-silico prediction, not a clinical call.

TJP2 p.Arg183Pro

c.548G>C · VCV3969090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1115 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1115	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 0.006
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	18.88	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

Grpmax group 0.00231% East Asian · 1/43,302 alleles

Overall 6.31e-05% 1/1,585,956 alleles · very rare exomes 1/1,433,600 · genomes 0/152,356 · joint denominator

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: TJP2
Protein: p.Arg183Pro
Coding: c.548G>C
MANE Select: NM_004817
Type: single nucleotide variant
Location: chr9:69221092 (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 183: 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.Arg183= Likely benign ★ same residue
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

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-arg183pro (accessed [today's date]).

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