Is TJP2 p.Arg900Cys (c.2698C>T) pathogenic?

TJP2 p.Arg900Cys (c.2698C>T) is classified Uncertain significance in TJP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.1558); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Arg900Cys (c.2698C>T)?

TJP2 p.Arg900Cys (c.2698C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Arg900Cys (c.2698C>T) in the general population?

TJP2 p.Arg900Cys (c.2698C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TJP2 p.Arg900Cys (c.2698C>T)?

AlphaMissense predicts likely benign (score 0.1558) — an in-silico prediction, not a clinical call.

TJP2 p.Arg900Cys

c.2698C>T · VCV3969108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1558	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -9.19	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 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	27.7	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 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00217% 35/1,613,020 alleles · ultra-rare exomes 30/1,460,838 · genomes 5/152,182 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
South Asian	0.0033%	30,327
European (non-Finnish)	0.00246%	40,668
Admixed American	0.00167%	59,966
African / African-American	0.00133%	74,920

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.Arg900Cys
Coding: c.2698C>T
MANE Select: NM_004817
Type: single nucleotide variant
Location: chr9:69248042 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.92 · 2 PDB

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.Arg900Ser Uncertain significance ★★ ⚠ 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-arg900cys (accessed [today's date]).

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