Is TANGO2 p.Phe6del (c.12CTT[1]) pathogenic?

TANGO2 p.Phe6del (c.12CTT[1]) is classified Uncertain significance in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). Very rare (popmax 0.004%, afr); Associated with recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome.

How common is TANGO2 p.Phe6del (c.12CTT[1]) in the general population?

TANGO2 p.Phe6del (c.12CTT[1]) is very rare (popmax 0.004%, afr) (gnomAD).

TANGO2 p.Phe6del

Q: What condition is associated with TANGO2 p.Phe6del (c.12CTT[1])?

TANGO2 p.Phe6del (c.12CTT[1]) is associated with recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (ClinVar).

Q: How is Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.12CTT[1] · rs1228744373 · VCV1312505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.3, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,046 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000205% 3/1,461,892 alleles · very rare

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.Phe6del
Coding: c.12CTT[1]
MANE Select: NM_152906
dbSNP: rs1228744373
Type: Microsatellite
Location: chr22:20036809 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 6: a β-strand; a UniProt-annotated variant site (in mecrcn; uncertain significance)

Full TANGO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

TANGO2 p.Phe6= Likely benign ★★ same residue
TANGO2 c.57-1743_*10769del Pathogenic ★★ same condition
TANGO2 c.57-1G>C Pathogenic/Likely pathogenic ★★ same condition
TANGO2 c.605+1G>A Pathogenic/Likely pathogenic ★★ same condition
TANGO2 c.711-3C>G Pathogenic/Likely pathogenic ★★ same condition
TANGO2 p.Arg140Ter Pathogenic ★★ same condition
TANGO2 p.Arg32Ter Pathogenic/Likely pathogenic ★★ same condition
TANGO2 p.Arg86Ter Pathogenic/Likely pathogenic ★★ 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/tango2-p-phe6del (accessed [today's date]).

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