TSC1 p.Pro548fs
c.1641_1642dup · VCV3728669
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
tuberous sclerosis 1
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 15 of 23 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TSC1
- Protein
- p.Pro548fs
- Coding
- c.1641_1642dup
- MANE Select
- NM_000368
- Type
- Microsatellite
- Location
- chr9:132905935 (GRCh38)
- Gene constraint
- LOEUF 0.227 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.55 · 5 PDB
- Residue 548
- the 'mediates interaction with wdr45b' region; the 'disordered' region; a UniProt-annotated variant site (in tsc1)
Disease context
tuberous sclerosis 1 — 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
- TSC1 p.Pro548Leu Uncertain significance ★★ ⚠ same residue
- TSC1 p.Pro548Ser Uncertain significance ★★ ⚠ same residue
- TSC1 p.Pro548= Likely benign ★ same residue
- TSC1 p.Arg424fs Pathogenic ★★ same condition
- TSC1 p.Gln109fs Pathogenic ★★ same condition
- TSC1 p.Gln301fs Pathogenic ★★ same condition
- TSC1 p.Glu636fs Pathogenic ★★ same condition
- TSC1 p.Gly443fs Pathogenic/Likely 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/tsc1-p-pro548fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown