NM_005089.3:c.758T>C (p.Val253Ala) is a missense variant in ZRSR2, a gene encoding a component of the minor spliceosome that is implicated in myelodysplastic syndromes, spliceosomopathies, and oral-facial-digital syndrome.¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting PM2 at supporting level.² The variant is absent from ClinVar, COSMIC, and CancerHotspots.org; no variant-specific functional data, segregation data, or de novo observations are available.³ SpliceAI predicts no significant splicing impact (max delta score 0.04). BayesDel add score is 0.527 (above the 0.27 damaging threshold), but as the sole predictor available, it does not meet the PP3 multiple-lines requirement.⁴ No publications in the literature packet mention the specific variant NM_005089.3:c.758T>C (p.Val253Ala). Five PMIDs reviewed for ZRSR2 gene-level context did not contain variant-specific data. PVS1 is not applicable as this is a missense variant not falling into the null-variant buckets of the ClinGen PVS1 decision framework (PMC6185798).⁵ Overall classification is limited by paucity of evidence. Only one supporting-level criterion (PM2) is met, which is insufficient to reach a Likely Pathogenic or Pathogenic classification under generic ACMG/AMP 2015 combination rules. No benign criteria are met.⁶