Is TANGO2 p.Ser263Pro (c.787T>C) pathogenic?

TANGO2 p.Ser263Pro (c.787T>C) is classified Uncertain significance in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.1733); Very rare (popmax 0.00333%, amr).

How common is TANGO2 p.Ser263Pro (c.787T>C) in the general population?

TANGO2 p.Ser263Pro (c.787T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TANGO2 p.Ser263Pro (c.787T>C)?

AlphaMissense predicts likely benign (score 0.1733) — an in-silico prediction, not a clinical call.

TANGO2 p.Ser263Pro

c.787T>C · rs1223483747 · VCV2183495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1733	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -12.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2.5, phastCons 0.07
Regional constraint	o/e 0.91	unconstrained · MANE · 28 kb · p 0.072 · regional, not allelic
Overall
CADD	13.38	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 0.00333% Admixed American · 2/60,014 alleles

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

Overall 0.000124% 2/1,614,152 alleles · very rare exomes 2/1,461,866 · genomes 0/152,286 · 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.Ser263Pro
Coding: c.787T>C
MANE Select: NM_152906
dbSNP: rs1223483747
Type: single nucleotide variant
Location: chr22:20064618 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB
Residue 263: a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; uncertain significance); a β-strand

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

Similar variants

TANGO2 p.Ser263= Benign/Likely benign ★★ same residue
TANGO2 p.Ser263Phe Uncertain significance ★ ⚠ 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-ser263pro (accessed [today's date]).

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