Accounting for human polymorphisms predicted to affect protein function

Genome Res. 2002 Mar;12(3):436-46. doi: 10.1101/gr.212802.


A major interest in human genetics is to determine whether a nonsynonymous single-base nucleotide polymorphism (nsSNP) in a gene affects its protein product and, consequently, impacts the carrier's health. We used the SIFT (Sorting Intolerant From Tolerant) program to predict that 25% of 3084 nsSNPs from dbSNP, a public SNP database, would affect protein function. Some of the nsSNPs predicted to affect function were variants known to be associated with disease. Others were artifacts of SNP discovery. Two reports have indicated that there are thousands of damaging nsSNPs in an individual's human genome; we find the number is likely to be much lower.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs / genetics
  • Amino Acid Motifs / physiology
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Chromosome Mapping / methods
  • Chromosome Mapping / standards
  • Chromosome Mapping / statistics & numerical data
  • Databases, Protein / statistics & numerical data
  • False Positive Reactions
  • Genes
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / physiology
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics
  • Proteins / physiology*
  • Pseudogenes / genetics
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / standards
  • Sequence Analysis, DNA / statistics & numerical data
  • Software


  • Proteins