Is TANGO2 p.Ser110Ala (c.328T>G) pathogenic?

TANGO2 p.Ser110Ala (c.328T>G) is classified Uncertain significance in TANGO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0683); Very rare (popmax 0.00153%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TANGO2 p.Ser110Ala (c.328T>G)?

TANGO2 p.Ser110Ala (c.328T>G) is associated with Inborn genetic diseases (ClinVar).

How common is TANGO2 p.Ser110Ala (c.328T>G) in the general population?

TANGO2 p.Ser110Ala (c.328T>G) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about TANGO2 p.Ser110Ala (c.328T>G)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

TANGO2 p.Ser110Ala

c.328T>G · rs150241211 · VCV1961809

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 28 kb · p 0.072 · regional, not allelic
Overall
CADD	22.1	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 0.00153% European (non-Finnish) · 18/1,179,916 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,614,052 alleles · very rare exomes 18/1,461,738 · genomes 0/152,314 · 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.Ser110Ala
Coding: c.328T>G
MANE Select: NM_152906
dbSNP: rs150241211
Type: single nucleotide variant
Location: chr22:20053499 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 110: a UniProt-annotated variant site (in mecrcn); an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TANGO2 p.Ser110= Likely benign ★ same residue
TANGO2 c.451+2T>A Pathogenic/Likely pathogenic ★★ same condition
TANGO2 p.Ala183Val Uncertain significance ★★ ⚠ same condition
TANGO2 p.Ala246Val Uncertain significance ★★ ⚠ same condition
TANGO2 p.Arg11Cys Uncertain significance ★★ ⚠ same condition
TANGO2 p.Arg180Pro Uncertain significance ★★ ⚠ same condition
TANGO2 p.Arg180Trp Uncertain significance ★★ ⚠ same condition
TANGO2 p.Arg230Cys Uncertain significance ★★ ⚠ 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-ser110ala (accessed [today's date]).

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