AlphaMissense
Classifies the pathogenicity of every possible single amino-acid substitution in the human proteome — 71 million missense variants — by fine-tuning AlphaFold on population variant frequencies; a resource for interpreting variants of uncertain significance.
At a glance
What it does
Provides a pathogenicity score (0–1) and a likely benign / ambiguous / likely pathogenic call per variant; the full prediction table is downloadable and integrated into variant annotation pipelines.
Notable uses in oncology
Classified 89% of all missense variants (32% likely pathogenic, 57% likely benign) versus ~0.1% annotated by human experts at the time; used as evidence in germline and tumour variant interpretation.
Tasks, data types and cancers
Architecture
Training data
AlphaMissense is an adaptation of AlphaFold fine-tuned on population frequency databases of human and primate variants. The authors state the model reaches its results on genetic and experimental benchmarks 'all without explicitly training on such data' — that is, without clinical pathogenicity labels as the training target; the training signal comes from which variants are observed, and at what frequency, in human and primate populations. ClinVar variants held out from training are used for evaluation (AUROC 0.94), not for training. Practical consequence for anyone reusing the model: the signal is oriented towards germline variation, so somatic driver status in a tumour is a different question and is not what the model was trained to answer.
Evaluation
| Benchmark / dataset | Metric | Value | External validation | Source |
|---|---|---|---|---|
| ClinVar held-out variants | AUROC | 0.94 (paper) | yes | Source |
How to run
Most users download the precomputed table rather than run the model; note the non-commercial licence on the predictions.
Regulatory status and intended use
Regulatory status is quoted from the source linked above and can change. Research-use-only models must not be used for clinical decisions.
Limitations and bias
- Missense only; no indels, splice or non-coding variants.
- Germline-oriented training signal; somatic driver status is a different question.
Sources
This page is educational — it is not medical advice and does not replace consultation with an oncologist. Diagnostic and treatment decisions are made solely by specialist physicians.