Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots” of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense muta¬tions can have a strong adverse effect on the cell and organ¬ism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells. It is commonly accepted that premature termination codons (PTCs) lead to the biosynthesis of truncated and usu¬ally inactive proteins. In addition, transcripts with PTC can be destroyed by a nonsense-mediated mRNA decay (NMD) machinery. We have considered the cell potentialities (gene families, diploidy, and alternative splicing) to overcome the worst consequences of nonsense mutation. As a special case, in the biosynthesis of a particular group of proteins called selenoproteins, the mutation CGA→UGA would not lead to the premature translation termination and NMD but rather to the insertion of selenocysteine or cysteine instead of former arginine. For the analysis of exonic DNA sequences, a special com¬puter program (called EPIMUT3) was developed, aimed to analyze CpG→TpG transitions in each of complementary DNA strands coupled with amino acid substitutions in the encoded protein. EPIMUT3 predicts methylation-dependent-nucleotide substitutions in the exon sequence as well as mutations in the encoded protein. After mutational substitutions are performed and the changes in DNA/protein sequences are visualized, the program is able to save the results in the format of Excel tables.