Is TANGO2 p.Arg88Ter (c.262C>T) pathogenic?

TANGO2 p.Arg88Ter (c.262C>T) is classified Pathogenic in TANGO2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-15). Ultra-rare (popmax 0.017%, afr); Associated with recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome.

How common is TANGO2 p.Arg88Ter (c.262C>T) in the general population?

TANGO2 p.Arg88Ter (c.262C>T) is ultra-rare (popmax 0.017%, afr) (gnomAD).

TANGO2 p.Arg88Ter

Q: What condition is associated with TANGO2 p.Arg88Ter (c.262C>T)?

TANGO2 p.Arg88Ter (c.262C>T) 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.262C>T · rs140115503 · VCV1312508

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, 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.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.1, phastCons 0.56
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% African / African-American · 12/70,582 alleles

Filtering AF 0.00974% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00763%

Overall 0.00144% 22/1,528,216 alleles · ultra-rare exomes 14/1,382,040 · genomes 8/146,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.017%	5,882
South Asian	0.0036%	27,811
European (non-Finnish)	0.000617%	162,080

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.Arg88Ter
Coding: c.262C>T
MANE Select: NM_152906
dbSNP: rs140115503
Type: single nucleotide variant
Location: chr22:20052581 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 88: a UniProt-annotated variant site (in mecrcn)

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.Arg88Gln Uncertain significance ★★ ⚠ same residue
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
TANGO2 p.Gln212Ter 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-arg88ter (accessed [today's date]).

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