SIFT score¶
SIFT estimates whether a missense variant may affect protein function. It compares the amino acid at that position with related proteins. A low score means the new amino acid is rarely tolerated in that alignment. It does not tell us whether a variant causes disease in a particular person.
Score range in Gene Inspector Pro¶
SIFT scores run from 0 to 1, but their direction is the reverse of several other predictors:
| Score | Prediction category |
|---|---|
| Below 0.05 | Predicted to affect protein function |
| 0.05 or higher | Predicted tolerated |
The 0.05 cutoff comes from the SIFT method. "Predicted tolerated" does not prove that a variant is harmless, and a low score does not establish clinical pathogenicity.
When it applies¶
SIFT is for single amino-acid substitutions. It does not provide functional predictions for synonymous, frameshift, untranslated-region, or most other types of variant. The prediction depends on a useful set of related protein sequences. Sparse or poorly matched alignments can make a score less reliable.
How to use it¶
Use SIFT as one clue about a missense change. Review it with other evidence, including population frequency, ClinVar submissions, the gene and disease mechanism, functional studies, inheritance, and genotype quality.