The detrimental missense mutations of HLA-B27 gene causing Ankylosing spondylitis were identified computationally and the substrate binding efficiencies of these mutations were analyzed. Out of 12 variants, IMutant 3.0, SIFT and PolyPhen programs identified 1 variant (Y83H) that was less stable, deleterious as well as damaging respectively. Modeling of this one variant was performed to understand the changes in their conformations with respect to the native HLA-B27 protein by computing their RMSD and Total energy. Furthermore the native and the variant were docked with beta-microglobulin to explain the binding efficiencies of those detrimental missense mutations.