Is TJP2 p.Ser196Arg (c.588C>A) pathogenic?

TJP2 p.Ser196Arg (c.588C>A) is classified Uncertain significance in TJP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.5329); Very rare (popmax 0.00942%, afr); Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Ser196Arg (c.588C>A)?

TJP2 p.Ser196Arg (c.588C>A) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Ser196Arg (c.588C>A) in the general population?

TJP2 p.Ser196Arg (c.588C>A) is very rare (popmax 0.00942%, afr) (gnomAD).

What do computational predictors say about TJP2 p.Ser196Arg (c.588C>A)?

AlphaMissense predicts ambiguous (score 0.5329) — an in-silico prediction, not a clinical call.

TJP2 p.Ser196Arg

c.588C>A · VCV4633153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00942%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5329	ambiguous
REVEL	0.039	moderately benign-leaning
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.62, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	20.9	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

Grpmax group 0.00942% African / African-American · 7/74,332 alleles

Filtering AF 0.0044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.000566% 9/1,588,916 alleles · very rare exomes 5/1,436,810 · genomes 4/152,106 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00942%	10,619
Admixed American	0.00176%	56,912
Remaining individualsnot grpmax-eligible	0.00163%	61,448

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.Ser196Arg
Coding: c.588C>A
MANE Select: NM_004817
Type: single nucleotide variant
Location: chr9:69221132 (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 196: 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.Ser196Ile 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-ser196arg (accessed [today's date]).

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