AlphaMissense score¶
AlphaMissense estimates the possible effect of a missense variant, a change that replaces one amino acid in a protein. It uses protein sequence context, predicted structural context, and population-frequency information. Its categories are computational predictions. They are not ACMG/AMP clinical classifications and do not diagnose a condition.
Score range in Gene Inspector Pro¶
AlphaMissense scores run from 0 to 1. The model's published high-precision categories are shown below.
| Score | Prediction category |
|---|---|
| Below 0.34 | Likely benign prediction |
| 0.34 to 0.564 | Ambiguous prediction |
| Above 0.564 | Likely pathogenic prediction |
The model developers selected the outer cutoffs to reach 90% precision on their ClinVar benchmark. The middle range is deliberately left ambiguous. These are model categories, not a final clinical interpretation for a person or a variant.
When it applies¶
AlphaMissense is for single amino-acid substitutions. It does not assess non-coding variants, splice changes, truncating variants, copy-number changes, or the full clinical meaning of a variant. Predictions can also differ in usefulness between genes and disease mechanisms.
How to use it¶
Use the score as one line of evidence for a missense variant. Check it with population frequency, ClinVar submissions, the gene and disease mechanism, inheritance, genotype quality, functional studies, and laboratory review. A high score does not establish pathogenicity, and a low score does not prove a variant is harmless.