Mechanisms of somatic mosaicism leading to GEI. Whether a somatic variant leads to immune dysregulation and a GEI requires that it impacts the encoded protein and is expressed in a relevant cell type. Additional genetic mechanisms that contribute to pathogenicity include: driver mutations that increase the variant allele frequency of passenger pathogenic immune variants, loss of heterozygosity of the healthy allele creating a homozygosity or hemizygosity, co-occurring germline or somatic variants in the same gene, and monoallelic expression or X-chromosome skewing with only expression of the mutant allele. Cellular mechanisms include a small subset of cells having a dominant impact on the immune response, a survival or proliferation advantage conferred by the somatic variant in a pathogenic cell type, and/or LOF in a subset of cells that impair the immune response in a clinically meaningful manner (created with https://Biorender.com).