Is TJP2 p.Pro71Gln (c.212C>A) pathogenic?

TJP2 p.Pro71Gln (c.212C>A) is classified Uncertain significance in TJP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1126); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with TJP2 p.Pro71Gln (c.212C>A)?

TJP2 p.Pro71Gln (c.212C>A) is associated with Inborn genetic diseases (ClinVar).

How common is TJP2 p.Pro71Gln (c.212C>A) in the general population?

TJP2 p.Pro71Gln (c.212C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TJP2 p.Pro71Gln (c.212C>A)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

TJP2 p.Pro71Gln

c.212C>A · VCV3456736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -7.33	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	GERP 1.3, phastCons 0.6
Regional constraint	o/e 0.98	unconstrained · MANE · 80 kb · p 0.53 · regional, not allelic
Overall
CADD	17.19	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 0.00133% African / African-American · 1/75,028 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,118 alleles · very rare exomes 4/1,461,872 · genomes 0/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,028
European (non-Finnish)	0.000254%	393,340

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.Pro71Gln
Coding: c.212C>A
MANE Select: NM_004817
Type: single nucleotide variant
Location: chr9:69216436 (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 71: the pdz 1 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.Pro71Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TJP2 p.Pro71= 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

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-pro71gln (accessed [today's date]).

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