Nonsynonymous single nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid changes in their corresponding proteins. Because nsSNPs can affect protein function, they are believed to have the largest impact on human health compared with SNPs in other regions of the genome. Therefore, it is important to distinguish those nsSNPs that affect protein function from those that are functionally neutral. Here we provide an overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein function. Most methods predict approximately 25-30% of human nsSNPs to negatively affect protein function, and such nsSNPs tend to be rare in the population. We discuss the utility of AAS prediction methods for Mendelian and complex diseases as well as their broader applications for understanding protein function.

中文翻译：

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预测氨基酸取代对蛋白质功能的影响。

非同义单核苷酸多态性（nsSNP）是在其相应蛋白质中引入氨基酸变化的编码变体。由于nsSNP可影响蛋白质功能，因此与基因组其他区域的SNP相比，它们被认为对人类健康的影响最大。因此，重要的是要区分那些影响蛋白质功能的nsSNP和那些功能中性的nsSNP。在这里，我们提供了氨基酸取代（AAS）预测方法的概述，该方法使用序列和/或结构来预测AAS对蛋白质功能的影响。大多数方法预测约有25-30％的人nsSNP对蛋白质功能产生负面影响，而此类nsSNP在人群中往往很少见。