NM_004260.3:c.2569_2574del (p.Cys857_Thr858del) is an in-frame deletion of 6 nucleotides in exon 15 of RECQL4, encoding a DNA helicase associated with Rothmund-Thomson syndrome (autosomal recessive) and cancer predisposition. This variant is present at high frequency in the general population: gnomAD v2.1 reports 1462 alleles out of 218,994 (0.67%) with 30 homozygotes, and a grpmax filtering allele frequency of 3.9% in the Admixed American population. gnomAD v4.1 reports 2479 alleles out of 1,574,460 (0.16%) with 41 homozygotes. The presence of 30 or more healthy homozygotes in population databases is incompatible with pathogenicity for a severe autosomal recessive disorder.¹ The variant meets BA1 (stand-alone benign): allele frequency exceeds 1% in the general population (grpmax FAF 3.9% in gnomAD v2.1). It also meets BS1 (strong benign): allele frequency exceeds 0.3% (global AF 0.67% in gnomAD v2.1), and BS2 (strong benign): 30 homozygotes are observed in a population database for a recessive disorder expected to be fully penetrant at an early age.² ClinVar reports this variant as Benign by 8 clinical laboratories and Likely benign by 1 laboratory (variation ID 135140), meeting BP6 (supporting benign).³ No pathogenic criteria are met. PVS1 is not applicable as this is an in-frame deletion, not a null variant. No functional data (PS3), segregation data (PP1), or case-control data (PS4) support pathogenicity. All in silico evidence (SpliceAI delta 0.00; REVEL/BayesDel unavailable for deletion variants) is neutral. PM2 is not met due to the variant's high population frequency.⁴ Classification: BENIGN. BA1 alone is sufficient for a benign classification per ACMG/AMP 2015 guidelines. The combination of BA1 + BS1 + BS2 + BP6 provides overwhelming evidence of benignity.⁵