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 (e.g. substitution from leucine to valine) has mild effect, and opposite. Similarly, if SNP disrupts secondary structure elements (e.g. 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:
* [http://sift-dna.org SIFT] This program provides insight into how a laboratory induced missense or nonsynonymous mutation will affect protein function based on physical properties of the amino acid and sequence homology.
* [https://gsponerlab.msl.ubc.ca/software/list/ LIST] (Local Identity and Shared Taxa) estimates the potential deleteriousness of mutations resulted from altering their protein functions. It is based on the assumption that variations observed in closely related species are more significant when assessing conservation compared to those in distantly related species.
* [https://rostlab.org/services/snap SNAP2]
* [http://www.sbg.bio.ic.ac.uk/suspect/index.html SuSPect]
* [http://genetics.bwh.harvard.edu/pph2/ PolyPhen-2]
* [http://loschmidt.chemi.muni.cz/predictsnp/ PredictSNP]
* MutationTaster: [http://www.mutationtaster.org/ official website]
* [http://www.ensembl.org/info/docs/tools/vep/index.html Variant Effect Predictor] from the Ensembl project
* [https://genomicscomputbiol.org/ojs3/GCB/article/view/48/182 SNPViz]  This program provides a 3D representation of the protein affected, highlighting the amino acid change so doctors can determine pathogenicity of the mutant protein.
* [http://provean.jcvi.org/index.php PROVEAN]
* [http://phyrerisk.bc.ic.ac.uk PhyreRisk] is a database which maps variants to experimental and predicted protein structures.
* [http://www.sbg.bio.ic.ac.uk/~missense3d/ Missense3D] is a tool which provides a stereochemical report on the effect of missense variants on protein structure.