The lupus risk SNP, R77H is unable to inhibit FcγRIIA function or its affinity for IgG, suggesting that this SNP affects the binding affinity of Mac-1 for FcγR likely by altering allostery relay to the αI-domain needed for productive binding, as we have described for Mac-1 binding to its canonical ligand, complement C330. Here, FCGR2A is linked to systemic lupus erythematosus.