<scp>MAVISp</scp> : A modular structure‐based framework for protein variant effects
Abstract The role of genomic variants in disease has expanded significantly with the advent of advanced sequencing techniques. The rapid increase in identified genomic variants has led to many variants being classified as Variants of Uncertain Significance or as having conflicting evidence, posing challenges for their interpretation and characterization. Additionally, current methods for predicting pathogenic variants often lack insights into the underlying molecular mechanisms. Here, we introduce MAVISp ( M ulti‐layered A ssessment of V ar I ants by S tructure for p roteins), a modular structural framework for variant effects, accompanied by a web server ( https://services.healthtech.dtu.dk/services/MAVISp-1.0/ ) to enhance data accessibility, consultation, and re‐usability. MAVISp currently provides data on over 1000 proteins, encompassing more than 10 million variants. A team of biocurators regularly analyzes and updates protein entries using standardized workflows, incorporating free‐energy calculations and biomolecular simulations. We illustrate the utility of MAVISp through selected case studies. The framework facilitates the analysis of variant effects at the protein level and has the potential to advance the understanding and application of mutational data in disease research.
Authors
- Anna Rohlin (ORCID: https://orcid.org/0000-0002-4083-6748)
- Laura L Bauer (ORCID: https://orcid.org/0000-0002-1435-8121)
- Ludovica Beltrame (ORCID: https://orcid.org/0000-0003-3855-1417)
- Lorenzo Favaro
- Simone Scrima (ORCID: https://orcid.org/0000-0002-5255-916X)
- Matteo Tiberti (ORCID: https://orcid.org/0000-0003-2529-3594)
- Burcu Aykaç Fas (ORCID: https://orcid.org/0000-0003-3842-731X)
- Anna Melidi
- Claudia Cava (ORCID: https://orcid.org/0000-0002-5540-4104)
- Matteo Arnaudi
- Kristine Degn (ORCID: https://orcid.org/0000-0002-3375-279X)
- Matteo Lambrughi (ORCID: https://orcid.org/0000-0002-0894-8627)
- Philipp Becker (ORCID: https://orcid.org/0009-0004-6253-0944)
- Mattia Utichi (ORCID: https://orcid.org/0000-0002-4918-458X)
- Peter Wad Sackett (ORCID: https://orcid.org/0000-0003-3628-2807)
- Valentina Sora (ORCID: https://orcid.org/0000-0002-6969-8174)
- Mef Nilbert (ORCID: https://orcid.org/0000-0003-2717-1937)
- Guglielmo Tedeschi (ORCID: https://orcid.org/0009-0000-9404-970X)
- Alberte Heering Estad
- Paraskevi Saridaki
- Terézia Dorčaková (ORCID: https://orcid.org/0009-0002-2137-5533)
- Joachim Breitenstein
- Karolina Krzesińska
- Francesca Maselli
- Jérémy Vinhas
- Eleni Kiachaki
- Anu Oswal
- Alberto Pettenella
- Katrine Meldgård
- Pablo Sánchez‐Izquierdo Besora
- Elena Papaleo
- Sumaiya Iqbal
- Jordan Safer
Institutions
- Broad Institute (US)
- Centre National de la Recherche Scientifique (FR)
- Lund University (SE)
- Université Paris Cité (FR)
- Istituto Universitario di Studi Superiori di Pavia (IT)
- Amager Hospital (DK)
- Sahlgrenska University Hospital (SE)
- Laboratoire de Biochimie Théorique (FR)
- Institute of Molecular Bioimaging and Physiology (IT)
- Danish Cancer Society (DK)
- University of Gothenburg (SE)
- University of Chemistry and Technology, Prague (CZ)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Protein Science
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1002/pro.70548
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Cooperation in Science and Technology
- Danmarks Grundforskningsfond
- LEO Fondet