TSC2 p.Phe123fs
c.369_372del · VCV4736494
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
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 | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 5 of 42 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.077 | GERP -3.3, phastCons 0.91 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TSC2
- Protein
- p.Phe123fs
- Coding
- c.369_372del
- MANE Select
- NM_000548
- Type
- Deletion
- Location
- chr16:2054326 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.81 · 2 PDB
- Residue 123
- an α-helix; the 'required for interaction with tsc1' region
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.Phe123Leu Uncertain significance ★ ⚠ same residue
- TSC2 p.Phe123= Likely benign ★ same residue
- TSC2 c.1945_1946+4del Pathogenic/Likely pathogenic ★★ same condition
- TSC2 c.2355+2_2355+5del Pathogenic ★★ same condition
- TSC2 c.5252_5259+19del Pathogenic/Likely pathogenic ★★ same condition
- TSC2 c.5259+1del Pathogenic/Likely pathogenic ★★ same condition
- TSC2 p.Ala1169fs Pathogenic ★★ same condition
- TSC2 p.Arg1032_Tyr1033insTer 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-phe123fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown