TANGO2 p.Ala158=
c.474G>A · rs781721580 · VCV2965548
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00447%, eas)
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 -6.3 | GERP -2.8 |
| Overall | ||
| CADD | 2.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00447%
East Asian · 2/44,774 alleles
Filtering AF
0.00074%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00054%
Overall
0.00112%
18/1,606,578 alleles · very rare
exomes 16/1,454,302 · genomes 2/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00447% | 22,387 |
| South Asian | 0.00224% | 44,720 |
| European (non-Finnish) | 0.00119% | 84,084 |
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.Ala158=
- Coding
- c.474G>A
- MANE Select
- NM_152906
- dbSNP
- rs781721580
- Type
- single nucleotide variant
- Location
- chr22:20061552 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.43 · 3 PDB
- Residue 158
- a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; delayed er-to-golgi transport; altered mitochondrial morphology); a β-strand
Similar variants
- TANGO2 p.Ala158Val Uncertain significance ★★ ⚠ same residue
- TANGO2 p.Ala158Thr 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
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-ala158 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown