Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by defects in the () gene. Although disease severity partially correlates with copy number, significant variability in disease severity and treatment response remains unexplained, prompting a search for additional biomarkers. Using native, long-read nanopore and targeted short-read bisulfite sequencing, we analyzed methylation patterns across the 30 kb gene. Our long-read analysis of 29 SMA patients identified tissue-specific variation in intronic regions and the 3'UTR. Further analysis of blood-derived DNA of 365 SMA patients identified no association between methylation and disease severity or treatment response, excluding blood-derived DNA methylation as a predictive biomarker. However, we discovered significant age-associated variation in methylation in intron 1 and the 3'UTR, suggesting a possible role in modifying SMN expression during development and aging. This study provides a framework for detailed methylation analysis in complex genetic regions.