TANGO2 p.Ala246=
c.738G>A · rs142558529 · VCV1543207
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, 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 -5.1 | GERP -2.5 |
| Overall | ||
| CADD | 0.406 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
European (non-Finnish) · 414/1,180,012 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0311%
Overall
0.0277%
447/1,614,136 alleles · ultra-rare
exomes 410/1,461,834 · genomes 37/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0351% | 2,850 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,682 |
| African / African-American | 0.00933% | 10,720 |
| South Asian | 0.00878% | 11,386 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
| Admixed American | 0.005% | 20,007 |
| East Asian | 0.00223% | 44,884 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
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
- TANGO2
- Protein
- p.Ala246=
- Coding
- c.738G>A
- MANE Select
- NM_152906
- dbSNP
- rs142558529
- Type
- single nucleotide variant
- Location
- chr22:20064569 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.43 · 3 PDB
- Residue 246
- a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; delayed er-to-golgi transport; altered mitochondrial morphology); a UniProt-annotated variant site (in mecrcn; uncertain significance)
Similar variants
- TANGO2 p.Ala246Val Uncertain significance ★★ ⚠ same residue
- TANGO2 c.451+2T>A Pathogenic/Likely pathogenic ★★ same type
- TANGO2 c.57-1G>C Pathogenic/Likely pathogenic ★★ same type
- TANGO2 c.605+1G>A Pathogenic/Likely pathogenic ★★ same type
- TANGO2 c.711-3C>G Pathogenic/Likely pathogenic ★★ same type
- TANGO2 p.Arg140Ter Pathogenic ★★ same type
- TANGO2 p.Arg32Ter Pathogenic/Likely pathogenic ★★ same type
- TANGO2 p.Arg86Ter Pathogenic/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/tango2-p-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown