Sniffles2 is an advanced tool for detecting structural variations (SVs) in long-read sequencing data, offering improved accuracy and speed compared to existing methods. It implements a repeat-aware clustering technique, fast consensus sequence, and coverage-adaptive filtering to enhance the detection of complex SVs. Sniffles2 is 11.8 times faster and 29% more accurate than state-of-the-art SV callers across different coverages, sequencing technologies, and SV types. The tool can generate fully genotyped VCF files for family and population-level SV calling, enabling the detection of mosaic SVs in bulk long-read data. In a study of 11 probands with *MECP2*-related disorders, Sniffles2 accurately identified causative SVs, including highly complex alleles with three overlapping SVs. Additionally, it detected multiple mosaic SVs in brain tissue from a patient with multiple system atrophy, highlighting the diversity of SVs within the cingulate cortex. Sniffles2 is open-source and available at https://github.com/fritzedazeck/Sniffles.Sniffles2 is an advanced tool for detecting structural variations (SVs) in long-read sequencing data, offering improved accuracy and speed compared to existing methods. It implements a repeat-aware clustering technique, fast consensus sequence, and coverage-adaptive filtering to enhance the detection of complex SVs. Sniffles2 is 11.8 times faster and 29% more accurate than state-of-the-art SV callers across different coverages, sequencing technologies, and SV types. The tool can generate fully genotyped VCF files for family and population-level SV calling, enabling the detection of mosaic SVs in bulk long-read data. In a study of 11 probands with *MECP2*-related disorders, Sniffles2 accurately identified causative SVs, including highly complex alleles with three overlapping SVs. Additionally, it detected multiple mosaic SVs in brain tissue from a patient with multiple system atrophy, highlighting the diversity of SVs within the cingulate cortex. Sniffles2 is open-source and available at https://github.com/fritzedazeck/Sniffles.