TJP2 p.Ala491=
c.1473C>A · rs138509345 · VCV288102
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, afr)
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 -0.65 | GERP -2.2 |
| Overall | ||
| CADD | 5.605 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
African / African-American · 35/74,892 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0303%
Overall
0.00273%
44/1,613,968 alleles · ultra-rare
exomes 24/1,461,846 · genomes 20/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0467% | 2,140 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| Admixed American | 0.005% | 19,999 |
| European (non-Finnish) | 8.47e-05% | 1,180,012 |
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.Ala491=
- Coding
- c.1473C>A
- MANE Select
- NM_004817
- dbSNP
- rs138509345
- Type
- single nucleotide variant
- Location
- chr9:69229203 (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 491
- the 'disordered' region
Similar variants
- 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
- TJP2 p.Gln207Ter Pathogenic/Likely pathogenic ★★ same type
- TJP2 p.Gln842Ter Pathogenic ★★ same type
- TJP2 p.Gln878Ter Likely 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-ala491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown