TSC2 p.Arg458Ter
c.1371_1372delinsTT · VCV4279972
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Rare
Conditions
1
tuberous sclerosis 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 42 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -3.9 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TSC2
- Protein
- p.Arg458Ter
- Coding
- c.1371_1372delinsTT
- MANE Select
- NM_000548
- Type
- Indel
- Location
- chr16:2062981 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.81 · 2 PDB
Disease context
tuberous sclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Tuberous sclerosis complex (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Taiwan, Province of China)
Similar variants
- TSC2 p.Arg458Pro Uncertain significance ★★ ⚠ same residue
- TSC2 p.Arg458= Likely benign ★★ same residue
- TSC2 p.Arg458Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- TSC2 p.Phe453Ter Pathogenic ★★ same condition
- TSC2 p.Ala675Leu Uncertain significance ★★ same condition
- TSC2 p.Glu1107Met Uncertain significance ★★ same condition
- TSC2 p.Glu1351Leu Uncertain significance ★★ same condition
- TSC2 p.Glu393Leu 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/tsc2-p-arg458ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown