Is TANGO2 p.Pro12fs (c.35_36del) pathogenic?

TANGO2 p.Pro12fs (c.3536del) is classified Pathogenic in TANGO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-21). Very rare (popmax 0.000169%, nfe).

How common is TANGO2 p.Pro12fs (c.35_36del) in the general population?

TANGO2 p.Pro12fs (c.35_36del) is very rare (popmax 0.000169%, nfe) (gnomAD).

TANGO2 p.Pro12fs

c.35_36del · rs1601975780 · VCV817318

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,048 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,124 alleles · very rare exomes 1/1,461,892 · genomes 1/152,232 · 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.Pro12fs
Coding: c.35_36del
MANE Select: NM_152906
dbSNP: rs1601975780
Type: Deletion
Location: chr22:20036833 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 3 PDB

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

Similar variants

TANGO2 p.Pro12= Likely benign ★ same residue
TANGO2 c.57-1743_*10769del Pathogenic ★★ same type
TANGO2 p.Cys2fs Pathogenic/Likely pathogenic ★★ same type
TANGO2 p.His94fs Pathogenic/Likely pathogenic ★★ same type
TANGO2 c.146-3605_451+2245del Pathogenic ★ same type
TANGO2 p.Glu53fs Pathogenic ★ same type
TANGO2 p.Ile190_Leu197del Likely pathogenic ★ same type
TANGO2 p.Lys166fs 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-pro12fs (accessed [today's date]).

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