Splice acceptors with the genomic NAGNAG motif may cause NAG insertion-deletions in transcripts, occur in 30% of human genes and are functional in at least 5% of human genes. We found five significant biases indicating that their distribution is nonrandom and that they are evolutionarily conserved and tissue-specific. Because of their subtle effects on mRNA and protein structures, these splice acceptors are often overlooked or underestimated, but they may have a great impact on biology and disease.