NM_004958.4:c.3610A>G (p.Ile1204Val) is a missense variant in the MTOR gene, which is associated with cerebral malformation via a gain-of-function mechanism (Brain Malformations CSPEC v1.1).¹ This variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2 at supporting strength under the Brain Malformations CSPEC.² No pathogenic or benign classifications exist in ClinVar; the variant has not been reported in any clinical or research database.³ No functional studies, case reports, de novo observations, or segregation data are available for this variant. OncoKB classifies the variant as Unknown Oncogenic Effect.⁴ The CSPEC framework marks 13 criteria as not applicable for MTOR variant assessment: PVS1 (GOF mechanism), PM6 (addressed under PS2), PP1 (mosaic/de novo), PP3 (LOF-focused algorithms), PP4 (accounted under PS4), PP5 (SVI recommendation), BS4 (de novo/mosaic), BP1 (LOF not mechanism), BP4 and BP7 (not applicable to missense), BP6 (SVI recommendation).⁵ With only one supporting-level pathogenic criterion (PM2_supporting) met and no benign criteria met, this variant is classified as a Variant of Uncertain Significance (VUS) under ACMG/AMP 2015 combination rules.⁶