The ZRSR2 c.812A>G (p.Tyr271Cys; p.Y271C) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in population databases and meeting PM2 at supporting strength.² Generic PVS1 is not supported because this is a missense substitution rather than a predicted null variant, although gene-level evidence supports loss of function as a disease mechanism for ZRSR2.³ Computational evidence is not sufficient for a definitive missense prediction: SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, while BayesDel is 0.588005.⁴