 The formation energies of native point defects in crystalline α-Al2O3 were investigated by combining first principles-based methods and theoretical models in a grand canonical framework. For defect formation reactions in this framework, the chemical potentials of chemical species and electrons can be constrained by the conditions of aqueous electrochemical systems, where liquid water is thermodynamically stable. Activation relaxation technique (ART) simulations using an empirical interatomic potential were implemented to discover candidates for stable configurations of point defects. Density functional theory (DFT) calculations were then used to confirm the accurate energetics of the candidate defect configurations. The results show that, except Al vacancies, the most stable defect configurations are generated by simply adding/removing atoms at particular high-symmetry sites. We also investigated the stability of these point defects as a function of the chemical potentials of both electron and oxygen. The results reveal that, at the conditions of thermodynamic stability for liquid water in aqueous electrochemical systems, Al vacancies as the most stable point defects in α-Al2O3 can be generated in exothermic defect formation reactions with negative formation energies. These thermodynamic tendencies provide critical insights into the nature of passive films formed under aqueous electrochemical conditions, particularly explaining of the formation of amorphous structures of passive alumina.