Polymorphism was crucial to research in ecological genetics by E. B. Ford and his co-workers from the mid-1920s to the 1970s (similar work continues today, especially on mimicry ). The results had a considerable effect on the mid-century evolutionary synthesis , and on present evolutionary theory . The work started at a time when natural selection was largely discounted as the leading mechanism for evolution,   continued through the middle period when Sewall Wright 's ideas on drift were prominent, to the last quarter of the 20th century when ideas such as Kimura 's neutral theory of molecular evolution was given much attention. The significance of the work on ecological genetics is that it has shown how important selection is in the evolution of natural populations, and that selection is a much stronger force than was envisaged even by those population geneticists who believed in its importance, such as Haldane and Fisher . 
An important group of SNPs are those that corresponds to missense mutations causing amino acid change on protein level. Point mutation of particular residue can have different effect on protein function (from no effect to complete disruption its function). Usually, change in amino acids with similar size and physico-chemical properties (. substitution from leucine to valine) has mild effect, and opposite. Similarly, if SNP disrupts secondary structure elements (. substitution to proline in alpha helix region) such mutation usually may affect whole protein structure and function. Using those simple and many other machine learning derived rules a group of programs for the prediction of SNP effect was developed:
equilibrium test calculator for biallelic markers (SNPs, indels etc),
including analysis for ascertainment bias for dominant/recessive models (due to biological or technial causes)
Enter observed counts for each genotype, then click "Calculate". (Copyright TRG, SR, INMD, 2008)
If you use this web-tool please cite:
Santiago Rodriguez, Tom R. Gaunt and Ian N. M. Day.
Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies.
American Journal of Epidemiology Advance Access published on January 6, 2009, DOI /aje/kwn359.