Structural brain malformations associated with Tuberous Sclerosis Complex (TSC) are related to the severity of the clinical symptoms and can be visualized by magnetic resonance imaging (MRI). Tuberous Sclerosis Complex is caused by inactivating TSC1 or TSC2 mutations. We investigated associations between TSC brain pathology and different inactivating TSC1 and TSC2 variants, and examined the potential prognostic value of subdivision of TSC2 variants based on their predicted effects on TSC2 expression. We performed genotype-phenotype associations of TSC-related brain pathology on a cohort of 64 children aged 1.4-17.9 years. Brain abnormalities were assessed using MRI. Individuals were grouped into those with an inactivating TSC1 variant and those with an inactivating TSC2 variant. The TSC2 group was subdivided into changes predicted to result in TSC2 protein expression (TSC2p) and changes predicted to prevent expression (TSC2x). The TSC2 group was associated with more and larger tubers, more radial migration lines, and more subependymal nodules than the TSC1 group. Subependymal nodules were also more likely to be calcified. Subdivision of the TSC2 group did not reveal additional, substantial differences, except for a larger number of tubers in the temporal lobe and a larger fraction of cystic tubers in the TSC2x subgroup. The severity of TSC-related brain pathology was related to the presence of an inactivating TSC2 variant. Although larger studies might find specific TSC2 variants that have prognostic value, in our cohort, subdivision of the TSC2 group did not lead to better prediction.