Is TSC2 p.Ile810fs (c.2429_2461delinsC) pathogenic?

TSC2 p.Ile810fs (c.24292461delinsC) is classified Pathogenic in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-29). Absent from gnomAD; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Ile810fs (c.2429_2461delinsC)?

TSC2 p.Ile810fs (c.2429_2461delinsC) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Ile810fs (c.2429_2461delinsC) in the general population?

TSC2 p.Ile810fs (c.2429_2461delinsC) 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 p.Ile810fs

c.2429_2461delinsC · rs878854082 · VCV237989

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 22 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.2, 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
Protein: p.Ile810fs
Coding: c.2429_2461delinsC
MANE Select: NM_000548
dbSNP: rs878854082
Type: Indel
Location: chr16:2074273 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 810: an α-helix

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

For Tuberous sclerosis complex (Orphanet):

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

Similar variants

TSC2 p.Ile810Val Benign/Likely benign ★★ same residue
TSC2 p.Ile810_Cys811delinsMetGly Uncertain significance ★ 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
TSC2 p.Gly1664Ala 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-ile810fs (accessed [today's date]).

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