Is TSC2 p.Ala306fs (c.916del) pathogenic?

TSC2 p.Ala306fs (c.916del) is classified Pathogenic in TSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-26). No gnomAD frequency available for this variant; Associated with tuberous sclerosis 2.

What condition is associated with TSC2 p.Ala306fs (c.916del)?

TSC2 p.Ala306fs (c.916del) is associated with tuberous sclerosis 2 (ClinVar).

How common is TSC2 p.Ala306fs (c.916del) in the general population?

TSC2 p.Ala306fs (c.916del) is no gnomAD frequency available for this variant (gnomAD).

How is Tuberous sclerosis complex inherited?

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

TSC2 p.Ala306fs

c.916del · rs2548495653 · VCV2747097

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 10 of 42
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.3	GERP -4.3

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.Ala306fs
Coding: c.916del
MANE Select: NM_000548
dbSNP: rs2548495653
Type: Deletion
Location: chr16:2058814 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.81 · 2 PDB
Residue 306: the 'required for interaction with tsc1' region

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.Ala306Ser Uncertain significance ★★ ⚠ same residue
TSC2 p.Ala306Val Uncertain significance ★★ same residue
TSC2 p.Ala306= Conflicting classifications of pathogenicity ★ same residue
TSC2 p.Ala306Pro Uncertain significance ★ ⚠ 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

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-ala306fs (accessed [today's date]).

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