In this research, the detrimental missense mutations of the proteins Mad1, BRAF and STK11 that cause various types of cancer and their structural variations upon mutation were analyzed computationally. The native Mad1 and the three mutants, viz., E511K, R556C and R556H; the native BRAF and the five mutants viz., I463S, K601E, L597R, R462I and V600E; the native STK11 and the five mutants, viz., D208N, G171S, G215D, P314H and P324L were analyzed to determine their geometrical deviations such as root mean square deviation, root mean square fluctuation, radius of gyration, potential energy and solvent accessible surface area, using conformational sampling technique. Additionally, the globally minimized structure of native and mutants was further analyzed to compute the distribution of secondary structure. Subsequently, docking studies were performed to determine their structural variations which in turn alter the complex formation of Mad1-Mad2, BRAFMEK1 and STK11-STRAD. The deleterious effect of the mutants would result in a comparative loss of enzyme function due to variations in their binding energy pertaining to spatial conformation and flexibility. Hence, the structural and functional variations exhibited in the mutantsof Mad1, BRAF and STK11 lead to pathogenesis.