NM_014225.5:c.739A>G (p.Thr247Ala) is a missense variant in exon 6 of PPP2R1A, a gene associated with autosomal dominant Houge-Janssens syndrome type 2 (neurodevelopmental disorder). PVS1 is not applicable as this is a missense variant that does not fall into null-variant categories.¹ This variant is absent from gnomAD v2.1 and gnomAD-Canada, and is present at an extremely low frequency in gnomAD v4.1 (1/1,610,866 alleles; AF = 6.21 × 10⁻⁷), satisfying PM2 at supporting strength.² Multiple in silico predictors do not support a deleterious effect: REVEL score is 0.285 (below pathogenic threshold of 0.5), BayesDel score is −0.185 (predicted benign), and SpliceAI predicts no splicing impact (max delta = 0.00), satisfying BP4 at supporting strength.³ No variant-specific functional studies, de novo reports, case-control data, segregation data, or ClinVar classifications exist for this variant. No pathogenic comparator variant at the same codon or residue has been identified. All remaining criteria are not met or not applicable.⁴ The only applicable criteria are PM2_supporting and BP4_supporting, which carry equal and opposite weight. Under the generic ACMG/AMP 2015 combination rules (PMID:25741868), one supporting pathogenic criterion and one supporting benign criterion cancel each other, resulting in a classification of Variant of Uncertain Significance (VUS).⁵