Gain-of-function (GOF) variants, which introduce new or amplify protein functions, are essential for understanding disease mechanisms. Despite advances in genomics and functional research, identifying and analyzing pathogenic GOF variants remains challenging owing to fragmented data and database limitations, underscoring the difficulty in accessing critical genetic information. To address this challenge, we manually reviewed the literature, pinpointing 3089 single-nucleotide variants and 72 insertions and deletions in 579 genes associated with 1299 diseases from 2069 studies, and integrated these with the 3.5 million predicted GOF variants. Our approach is complemented by a proprietary scoring system that prioritizes GOF variants on the basis of the evidence supporting their GOF effects and provides predictive scores for variants that lack existing documentation. We then developed a database named GoFCards for general geneticists and clinicians to easily obtain GOF variants in humans (http://www.genemed.tech/gofcards). This database also contains data from >150 sources and offers comprehensive variant-level and gene-level annotations, with the aim of providing users with convenient access to detailed and relevant genetic information. Furthermore, GoFCards empowers users with limited bioinformatic skills to analyze and annotate genetic data, and prioritize GOF variants. GoFCards offers an efficient platform for interpreting GOF variants and thereby advancing genetic research.<br /> [GRAPHICS] .