Is TSC2 p.Glu366Arg (c.1096_1097delinsCG) pathogenic?

TSC2 p.Glu366Arg (c.10961097delinsCG) is classified Uncertain significance in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). Associated with hereditary neoplastic syndrome.

What condition is associated with TSC2 p.Glu366Arg (c.1096_1097delinsCG)?

TSC2 p.Glu366Arg (c.1096_1097delinsCG) is associated with hereditary neoplastic syndrome (ClinVar).

TSC2 p.Glu366Arg

c.1096_1097delinsCG · VCV3462567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 37 kb · p 0.88 · regional, not allelic

Variant & gene context

Gene: TSC2
Protein: p.Glu366Arg
Coding: c.1096_1097delinsCG
MANE Select: NM_000548
Type: Indel
Location: chr16:2060790 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 366: an α-helix; the 'required for interaction with tsc1' region

Full TSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TSC2 p.Glu366Ala Uncertain significance ★ ⚠ same residue
TSC2 p.Glu366Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Glu366Gly Uncertain significance ★ ⚠ same residue
TSC2 p.Glu366Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
TSC2 p.Glu366Val Uncertain significance ★ same residue
TSC2 p.Glu366Ter Pathogenic ★★ same residue
TSC2 p.Phe453Ter Pathogenic ★★ same condition
TSC2 p.Val827fs Pathogenic ★★ 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/tsc2-p-glu366arg (accessed [today's date]).

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