Mosaic mutations acquired during early embryogenesis can lead to severe early-onset genetic disorders and cancer predisposition, but are often undetectable in blood samples. The rate and mutational spectrum of embryonic mosaic mutations (EMMs) have only been studied in few selected tissues and their contribution to genetic disorders is unknown. For this reason, we investigated how frequent mosaic mutations occur during embryogenesis across all germ layers and tissues. Using RNA sequencing (RNA-seq) data from the Genotype-Tissue Expression (GTEx) cohort comprising 49 tissues and 570 individuals, we found that new-borns on average harbour 0.5 – 1 post-zygotic and early embryonic mosaic mutations in coding exons affecting multiple tissues and organs (rate of 1.3225× 10−8 per nucleotide per individual). We further observed that EMMs are dominated by a mutational signature associated with spontaneous deamination of methylated cytosines and the number of cell divisions. Our findings suggest that EMMs are as frequent…