Abstract
Genetic variations (including substitutions, insertions, and deletions) exert a profound influence on DNA sequences. These variations are systematically classified as synonymous, nonsynonymous, and nonsense, each manifesting distinct effects on proteins. The implementation of high-throughput sequencing has significantly augmented our comprehension of the intricate interplay between gene variations and protein structure and function, as well as their ramifications in the context of diseases. Frameshift variations, particularly small insertions and deletions (indels), disrupt protein coding and are instrumental in disease pathogenesis. This review presents a succinct review of computational methods, databases, current challenges, and future directions in predicting the consequences of coding frameshift small indels variations. We analyzed the predictive efficacy, reliability, and utilization of computational methods and variant account, reliability, and utilization of database. Besides, we also compared the prediction methodologies on GOF/LOF pathogenic variation data. Addressing the challenges pertaining to prediction accuracy and cross-species generalizability, nascent technologies such as AI and deep learning harbor immense potential to enhance predictive capabilities. The importance of interdisciplinary research and collaboration cannot be overstated for devising effective diagnosis, treatment, and prevention strategies concerning diseases associated with coding frameshift indels variations.