TSC2 p.Phe239fs
c.716_719del · VCV3381867
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
3
lymphangioleiomyomatosis
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 8 of 42 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -3.7, phastCons 0.002 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TSC2
- Protein
- p.Phe239fs
- Coding
- c.716_719del
- MANE Select
- NM_000548
- Type
- Deletion
- Location
- chr16:2056710 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.81 · 2 PDB
- Residue 239
- an α-helix; the 'required for interaction with tsc1' region
Disease context
lymphangioleiomyomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: isolated focal cortical dysplasia type IItuberous sclerosis 2
For Perivascular epithelioid cell neoplasm (Orphanet):
- Onset
- Adolescent, Adult, Childhood, Elderly
Similar variants
- TSC2 p.Phe239Cys Benign/Likely benign ★★ ⚠ same residue
- TSC2 p.Phe239= Conflicting classifications of pathogenicity ★ 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-phe239fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown