Is TJP2 p.Pro119= (c.357C>T) pathogenic?

TJP2 p.Pro119= (c.357C>T) is classified Likely benign in TJP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-12). Very rare (popmax 0.00686%, nfe).

How common is TJP2 p.Pro119= (c.357C>T) in the general population?

TJP2 p.Pro119= (c.357C>T) is very rare (popmax 0.00686%, nfe) (gnomAD).

TJP2 p.Pro119=

c.357C>T · rs753087955 · VCV3032398

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00686%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP 0.28, phastCons 0.014
Overall
CADD	8.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00686% European (non-Finnish) · 81/1,180,044 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00509% 82/1,612,192 alleles · very rare exomes 81/1,459,950 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00686%	14,568
Remaining individualsnot grpmax-eligible	0.0016%	62,318

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.Pro119=
Coding: c.357C>T
MANE Select: NM_004817
dbSNP: rs753087955
Type: single nucleotide variant
Location: chr9:69220901 (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 119: the pdz 1 domain

Full TJP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TJP2 p.Pro119His Uncertain significance ★ ⚠ same residue
TJP2 p.Pro119Leu Uncertain significance ★ ⚠ same residue
TJP2 p.Pro119Thr Uncertain significance ★ ⚠ same residue
TJP2 c.239+1G>A Pathogenic/Likely pathogenic ★★ same type
TJP2 p.Arg412Ter Pathogenic ★★ same type
TJP2 p.Arg591Ter Pathogenic ★★ same type
TJP2 p.Arg632Ter Pathogenic ★★ same type
TJP2 p.Arg725Ter Pathogenic ★★ same type

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-pro119 (accessed [today's date]).

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