Is TJP2 p.Val779Met (c.2335G>A) pathogenic?

TJP2 p.Val779Met (c.2335G>A) is classified Uncertain significance in TJP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-08-07). AlphaMissense: likely pathogenic (0.8274); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Val779Met (c.2335G>A)?

TJP2 p.Val779Met (c.2335G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Val779Met (c.2335G>A) in the general population?

TJP2 p.Val779Met (c.2335G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about TJP2 p.Val779Met (c.2335G>A)?

AlphaMissense predicts likely pathogenic (score 0.8274) — an in-silico prediction, not a clinical call.

TJP2 p.Val779Met

c.2335G>A · rs145368713 · VCV502683

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8274 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8274	likely pathogenic
REVEL	0.303	indeterminate
SaProt	LLR -10.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0118% 190/1,613,784 alleles · ultra-rare exomes 169/1,461,480 · genomes 21/152,304 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Admixed American	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0224%	4,463
East Asian	0.0201%	4,987
European (non-Finnish)	0.0113%	8,870
African / African-American	0.008%	12,507
Finnishnot grpmax-eligible	0.00312%	32,004

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.Val779Met
Coding: c.2335G>A
MANE Select: NM_004817
dbSNP: rs145368713
Type: single nucleotide variant
Location: chr9:69238769 (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 779: the guanylate kinase-like domain

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-val779met (accessed [today's date]).

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