Scalable sequence–function studies have enabled the systematic analysis and cataloging of
hundreds of thousands of coding and noncoding genetic variants in the human genome …

The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …

Predicting the effects of mutations in proteins is critical to many applications, from
understanding genetic disease to designing novel proteins to address our most pressing …

Hypermobility involves excessive flexibility and systemic manifestations of connective tissue
fragility. We propose a folate-dependent hypermobility syndrome model based on clinical …

The assessment of variant effect predictor (VEP) performance is fraught with biases
introduced by benchmarking against clinical observations. In this study, building on our …

The success of personalized genomic medicine depends on our ability to assess the
pathogenicity of rare human variants, including the important class of missense variation …

Background Glucokinase (GCK) regulates insulin secretion to maintain appropriate blood
glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic …

Background Genetic variation in the human genome is a major determinant of individual
disease risk, but the vast majority of missense variants have unknown etiological effects …

To maintain genome integrity, cells must accurately duplicate their genome and repair DNA
lesions when they occur. To uncover genes that suppress DNA damage in human cells, we …

Predicting the effects of mutations in proteins is critical to many applications, from
understanding genetic disease to designing novel proteins that can address our most …