NM_000548.5:c.729C>G (p.Leu243=) is a synonymous variant in exon 8 of TSC2 with an overall allele frequency of 0.316-0.355% in gnomAD, exceeding the BS1 threshold of >0.3%.¹ This variant has been observed in 10 homozygous individuals in gnomAD v4.1 among 1,612,278 alleles, constituting strong evidence for benignity in a dominant disorder (BS2).² SpliceAI predicts no splice impact (max delta = 0.01), and the variant is synonymous with no predicted effect on protein sequence, supporting multiple benign computational evidence lines (BP4, BP7).³ ClinVar classifies this variant as Benign/Likely benign across 21 clinical laboratory submissions (15 Benign, 6 Likely benign), with criteria provided and no conflicting pathogenic interpretations (BP6).⁴ No pathogenic criteria are met. PVS1, PS1, and PM5 are not applicable to this synonymous variant. PS2, PS3, PS4, PS5, PM1, PM2, PM6, PP3, and PP5 are not met. PP1, PP4, BS4, BP2, and BP5 are not assessed due to absence of data. BA1 is not met (overall AF <1%). BP1 and PP2 are not applicable to synonymous variants.⁵ Applying generic ACMG/AMP 2015 final combination rules: two strong benign criteria (BS1, BS2) alone satisfy the classification threshold for Benign. Additionally, three supporting benign criteria (BP4, BP6, BP7) reinforce the benign classification.⁶