Ataxia telangiectasia-mutated (ATM) protein kinase, a key player in cellular integrity regulation, is known for its role in DNA damage response. This study investigates the broader impact of ATM on cellular processes and potential clinical manifestations arising from mutations, aiming to expand our understanding of ATM's diverse functions beyond conventional roles. The research employs a comprehensive set of computational techniques for a thorough analysis of ATM mutations. The mutation data are curated from dbSNP and HuVarBase databases. A meticulous assessment is conducted, considering factors such as deleterious effects, protein stability, oncogenic potential, and biophysical characteristics of the identified mutations. Conservation analysis, utilizing diverse computational tools, provides insights into the evolutionary significance of these mutations. Molecular docking and dynamic simulation analyses are carried out for selected mutations, investigating their interactions with Y2080D, AZD0156, and quercetin inhibitors to gauge potential therapeutic implications. Among the 419 mutations scrutinized, five (V1913C, Y2080D, L2656P, C2770G, and C2930G) are identified as both disease causing and protein destabilizing. The study reveals the oncogenic potential of these mutations, supported by findings from the COSMIC database. Notably, Y2080D is associated with haematopoietic and lymphoid cancers, while C2770G shows a correlation with squamous cell carcinomas. Molecular docking and dynamic simulation analyses highlight strong binding affinities of quercetin for Y2080D and AZD0156 for C2770G, suggesting potential therapeutic options. In summary, this computational analysis provides a comprehensive understanding of ATM mutations, revealing their potential implications in cellular integrity and cancer development. The study underscores the significance of Y2080D and C2770G mutations, offering valuable insights for future precision medicine targeting-specific ATM. Despite informative computational analyses, a significant research gap exists, necessitating essential in vitro and in vivo studies to validate the predicted effects of ATM mutations on protein structure and function.