When things go wrong, we can see how very sensitive the shape of a protein is to being disrupted. It is obvious that for the protein to work it not only has to have the correct sequence of amino acids, but also it has to be folded exactly right.
For example [from Jennifer Doudna and Samuel Sternberg. 2017. A Crack in Creation.] p. 13. “[I]n sickle cell disease, a genetic disorder in the blood, the seventeenth letter [nucleotide] of a gene known as beta-globulin is mutated from an A to T. When translated into amino acids, this mutation results in an amino acid glutamate being replaced by the amino acid valine in a critical region of the hemoglobin protein, the major oxygen-transporting component of red blood cells.” When an individual inherits two copies of this gene, one from each parent (double recessive condition), that person is seriously affected and could die. Yet this change in the gene is so small, just one nucleotide substituted for another (a SNP).
p. 14 Other genetic diseases exhibit dominant inheritance, meaning that just a single copy of the mutated gene is enough to cause the disease. One example is WHIM syndrome, in which the one thousandth letter of the CXCR4 gene is mutated from a C to a T.
14 Conversely, deletions are the culprit in the most common type of cystic fibrosis … [where]the deletion of three letters of genetic code in the CFTR gene results in a protein that lacks an important amino acid and does not function properly.