Is TANGO2 p.Ala202Val (c.605C>T) pathogenic?

TANGO2 p.Ala202Val (c.605C>T) is classified Uncertain significance in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-11). AlphaMissense: likely benign (0.1121); Very rare (popmax 0.00137%, afr).

How common is TANGO2 p.Ala202Val (c.605C>T) in the general population?

TANGO2 p.Ala202Val (c.605C>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about TANGO2 p.Ala202Val (c.605C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

TANGO2 p.Ala202Val

c.605C>T · rs2048412055 · VCV1472429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.87	donor gain · deltas
Pangolin	Δ0.76	gain · loss 0.45 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 28 kb · p 0.072 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,088 alleles

Overall 0.000129% 2/1,545,986 alleles · very rare exomes 1/1,393,760 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,088
European (non-Finnish)	8.74e-05%	1,144,128

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.Ala202Val
Coding: c.605C>T
MANE Select: NM_152906
dbSNP: rs2048412055
Type: single nucleotide variant
Location: chr22:20061683 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 202: a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; delayed er-to-golgi transport; altered mitochondrial morphology)

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

Similar variants

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
TANGO2 p.Arg88Ter 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-ala202val (accessed [today's date]).

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