Notably, the protective coding SNP rs72824905, leading to the gain‐of‐function p.P522R substitution in PLCG2, provides proof of concept that only a limited increase in immune activation translates to a beneficial effect, as stronger gain‐of‐function mutations in PLCG2 (e.g., p.S707Y and p.L848P) are associated with autoimmune disorders such as PLCγ2‐associated antibody deficiency and immune dysregulation syndrome (PLAID) and autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID).13, 43, 44. This evidence concerns the gene PLCG2 and agammaglobulinemia.