SIFT
Description: SIFT predicts if an amino acid substitution is deleterious to protein function. SIFT can be applied to nonsynonymous polymorphisms and missense mutations. Mutations can be submitted for prediction.
Keywords: nonsynonymous,polymorphism,amino acid,substitution,missense,mutation

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Sorting Intolerant From Tolerant

at the Fred Hutchinson Cancer Research Center.
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SIFT predicts whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids. SIFT can be applied to naturally occurring nonsynonymous polymorphisms and laboratory-induced missense mutations.
Given a protein sequence, SIFT will return predictions for what amino acid substitutions will affect protein function.
SIFT is a multistep procedure that:
(1) searches for and chooses similar sequences
(2) makes an alignment of these sequences
(3) calculates scores based on the amino acids appearing at each position in the alignment.
You can:
submit a dbSNP id (SNPs from multiple proteins, 2 minutes)
-or- submit a GI # (2 minutes)
-or- submit a protein sequence (10-15 minutes)
-or- submit a query sequence along with related sequences (< 1 minute)
-or- submit alignment of your query sequence with related sequences (< 1 minute)
-or submit a block
SIFT for in-house use (version 3.0, released March 21, 2008):
Copyright code & exe (Sun, Linux) Report bugs
Prediction on human SNPs (Genome Research 12: 436-446 pdf)
Initial training/test sets for SIFT: LacI, Lysozyme, HIV protease
Other prediction tools for amino acid substitutions: PolyPhen , MAPP , SNPs3D, PMut
Many prediction tools have been developed since SIFT was first published it 2001. MAPP, SNPs3D, and PMut are three methods that have been shown to perform better than SIFT in their published results.
- SNPs3D is great for fast retrieval of predictions of nsSNPs from dbSNP
- MAPP is great if you only have one or two proteins to predict on
Our review "Predicting the Effects of Amino Acid Substitutions on Protein Function" in Annual Review of Genomics and Human Genetics:
Chapter
Supplementary Table 1
Citation
Referencing SIFT
version 1 (pdf), version 2 (pdf)
SIFT help page
About the author

Page last modified January 2007