Is TSC2 c.5259+1del pathogenic?

TSC2 c.5259+1del is classified Pathogenic/Likely pathogenic in TSC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-11-07). Absent from gnomAD; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 c.5259+1del?

TSC2 c.5259+1del is associated with tuberous sclerosis 2, tuberous sclerosis (ClinVar).

How common is TSC2 c.5259+1del in the general population?

TSC2 c.5259+1del is absent from gnomAD (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TSC2 c.5259+1del

rs137854317 · VCV49417

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

tuberous sclerosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 0.48, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TSC2
Coding: c.5259+1del
MANE Select: NM_000548
dbSNP: rs137854317
Type: Deletion
Location: chr16:2088324 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB

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

Disease context

tuberous sclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tuberous sclerosis

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

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 p.Ala1169fs Pathogenic ★★ same condition
TSC2 p.Arg1032_Tyr1033insTer Pathogenic ★★ same condition
TSC2 p.Arg1459fs Pathogenic ★★ same condition
TSC2 p.Arg691fs Pathogenic ★★ same condition
TSC2 p.Asp1126fs 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-c-5259-plus-1del (accessed [today's date]).

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