TYK2 and rheumatoid arthritis: Although, W620R of PTPN22, D358A of IL6R and P1104A of TYK2 variants are known to have very strong genome wide significant associations (≥P-value threshold of 5 × 10−8) with the RA risk, computational methods like SIFT, Polyphen-2, CADD, and FATHMM have predicted them to be non-deleterious.