The map recapitulates known regions important for function (except partially the histone interacting PHD1 domain), provides evidence to guide clinical variant interpretation for APS-1, supports a genotype-phenotype correlation in an international patient cohort, associates apparently-damaging variants with hypoparathyroidism and vitamin B12 deficiency anemia in the UK BioBank, and allows for confident classification of 32% of VUS. This evidence concerns the gene AIRE and hypoparathyroidism.