Is TANGO2 p.Ser127= (c.381C>T) pathogenic?

TANGO2 p.Ser127= (c.381C>T) is classified Likely benign in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with TANGO2 p.Ser127= (c.381C>T)?

TANGO2 p.Ser127= (c.381C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TANGO2 p.Ser127= (c.381C>T) in the general population?

TANGO2 p.Ser127= (c.381C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

TANGO2 p.Ser127=

c.381C>T · rs1471455689 · VCV3173751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.5, phastCons 0.99
Overall
CADD	15.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,528 alleles · very rare exomes 3/1,461,324 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.00017%	589,786

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.Ser127=
Coding: c.381C>T
MANE Select: NM_152906
dbSNP: rs1471455689
Type: single nucleotide variant
Location: chr22:20055943 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 127: a UniProt-annotated variant site (in mecrcn)

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 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
TANGO2 p.Arg230His 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-ser127 (accessed [today's date]).

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