Variant effects on protein structure

The effects of variants on protein structure can vary dramatically depending on the type of protein and the extent of variation.

Take, for instance, a large, multi-domain protein with multiple variants. One variant could involve the deletion of a large region of protein sequence, corresponding to an individual domain. If the core function of these domains are independent, the function of the remaining domains may not be affected at all. Another variant of this protein, however, may involve the changing of only a single amino acid in the protein sequence.  

Despite the relative insignificance of this change to the overall protein sequence, if this residue is key to the function of the protein (for instance at the active site of an enzyme) then this could completely eradicate protein function, or modify it in some way, for instance to change the specificity of an enzyme.

For further reading on this, please see this paper by Studer RA et al8.