Published in

American Association for the Advancement of Science, Science, 6648(380), 2023

DOI: 10.1126/science.abn8197



Export citation

Search in Google Scholar

The landscape of tolerated genetic variation in humans and primates

Journal article published in 2023 by Hong Gao ORCID, Tobias Hamp, Jeffrey Ede, Joshua G. Schraiber, Jeremy McRae ORCID, Moriel Singer-Berk ORCID, Yanshen Yang, Anastasia S. D. Dietrich ORCID, Petko P. Fiziev ORCID, Lukas F. K. Kuderna ORCID, Laksshman Sundaram ORCID, Yibing Wu, Aashish Adhikari ORCID, Yair Field ORCID, Chen Chen and other authors.
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

Full text: Unavailable

Green circle
Preprint: archiving allowed
Green circle
Postprint: archiving allowed
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO


Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.