Is TANGO2 p.Val100Met (c.298G>A) pathogenic?

TANGO2 p.Val100Met (c.298G>A) is classified Uncertain significance in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: likely benign (0.084); Very rare (popmax 0.00446%, eas).

How common is TANGO2 p.Val100Met (c.298G>A) in the general population?

TANGO2 p.Val100Met (c.298G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about TANGO2 p.Val100Met (c.298G>A)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

TANGO2 p.Val100Met

c.298G>A · rs772019892 · VCV1416439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -1.9
Regional constraint	o/e 0.91	unconstrained · MANE · 28 kb · p 0.072 · regional, not allelic
Overall
CADD	11.8	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 0.00446% East Asian · 2/44,872 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00105% 17/1,613,742 alleles · very rare exomes 15/1,461,538 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,436
African / African-American	0.00133%	74,928
European (non-Finnish)	0.0011%	90,751
South Asian	0.0011%	91,084

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.Val100Met
Coding: c.298G>A
MANE Select: NM_152906
dbSNP: rs772019892
Type: single nucleotide variant
Location: chr22:20053469 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 100: a UniProt-annotated variant site (in mecrcn)

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

Similar variants

TANGO2 p.Val100Leu Uncertain significance ★★ ⚠ same residue
TANGO2 p.Val100= 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

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-val100met (accessed [today's date]).

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