Is TANGO2 p.Asp187Tyr (c.559G>T) pathogenic?

TANGO2 p.Asp187Tyr (c.559G>T) is classified Uncertain significance in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-11). AlphaMissense: likely benign (0.2951); Very rare (popmax 0.000693%, nfe).

How common is TANGO2 p.Asp187Tyr (c.559G>T) in the general population?

TANGO2 p.Asp187Tyr (c.559G>T) is very rare (popmax 0.000693%, nfe) (gnomAD).

What do computational predictors say about TANGO2 p.Asp187Tyr (c.559G>T)?

AlphaMissense predicts likely benign (score 0.2951) — an in-silico prediction, not a clinical call.

TANGO2 p.Asp187Tyr

c.559G>T · rs762538745 · VCV2163891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000693%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2951	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -12.95	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.45	donor gain · deltas
Pangolin	Δ0.24	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 28 kb · p 0.072 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000693% European (non-Finnish) · 8/1,154,906 alleles

Filtering AF 0.000298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.000511% 8/1,566,208 alleles · very rare exomes 7/1,413,940 · genomes 1/152,268 · joint denominator

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.Asp187Tyr
Coding: c.559G>T
MANE Select: NM_152906
dbSNP: rs762538745
Type: single nucleotide variant
Location: chr22:20061637 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 187: a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; delayed er-to-golgi transport; altered mitochondrial morphology); an α-helix

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

Similar variants

TANGO2 p.Asp187= Likely benign ★ 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-asp187tyr (accessed [today's date]).

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