Limitations

This study has several limitations. First, functional studies (e.g., patch-clamp, calcium imaging) were not performed to validate the functional impact of the variant. Second, the patient declined family screening, so the origin of the variant could not be determined. Third, available cryo-EM structures lack the N-terminal region containing Pro44; therefore, the AlphaFold-predicted structure awaits experimental validation. Fourth, the follow-up period is relatively short (21 months), and long-term prognosis requires further observation. Despite these limitations, the extreme rarity, evolutionary conservation, surface-exposed location, and phenotypic consistency suggest that this variant could be a candidate susceptibility variant for FSGS. However, the clinical phenotypic association suggested by this case should not be equated with definitive molecular pathogenic validation, which would require functional and familial segregation studies.