NM_032444.3:c.903G>C (p.Lys301Asn) is a missense variant in SLX4, a Fanconi anemia gene (FANCP) where biallelic loss-of-function variants are the established disease mechanism. As a missense change, PVS1 is not applicable.¹ The variant is present at extremely low frequency in population databases: gnomAD v2.1 (1/31,392 alleles, AF 0.0032%) and gnomAD v4.1 (1/1,614,028 alleles, AF 0.00006%), meeting PM2 at supporting level for rarity below the 0.1% threshold.² Multiple in silico predictors consistently support a benign effect: REVEL 0.148 (benign), BayesDel -0.375 (neutral), and SpliceAI max delta 0.01 (no splicing impact), meeting BP4 at supporting benign level.³ SLX4 is a gene where primarily truncating variants cause Fanconi anemia (FANCP); as a missense variant in a gene where the primary pathogenic mechanism is loss of function, BP1 applies at supporting benign level.⁴ The variant is absent from ClinVar and has not been reported as pathogenic by any reputable source. No variant-specific functional studies, case-control data, segregation data, or de novo observations are available.⁵ The evidence is limited and conflicting: one supporting pathogenic criterion (PM2) and two supporting benign criteria (BP1, BP4). Under ACMG/AMP 2015 rules, the variant is classified as a Variant of Uncertain Significance (VUS).⁶