The most deleterious missense mutations of angiogenin forming Amyotrophic lateral sclerosis were identified computationally and the substrate binding efficiencies of these mutations were also analyzed. Out of 12 variants, IMutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. These 3 variants were modeled to find their conformational changes in concern with native angiogenin through RMSD calculation and Total energy. Docking of native and 3 mutants with ribonuclease inhibitor was performed to describe the binding efficiencies of those detrimental missense mutations. By computing the binding amino acids' flexibility of angiogenin and computing the binding free energy (ΔG) between native and mutant complexes, the loss in binding affinity with their interacting protein namely ribonuclease inhibitor was investigated.