NM_080605.4:c.902_905dup is a 4bp duplication producing a frameshift predicted to yield NP_542172.2:p.(Glu303AlafsTer141) in B3GALT6, a gene where loss of function is an established disease mechanism for autosomal recessive Ehlers-Danlos-syndrome-like connective tissue disorder (PVS1_Moderate; PMID:23664118, PMC6185798). The NM_080605.4 transcript is MANE Select and represents the single exon of B3GALT6; nonsense-mediated decay is not expected, warranting a downgrade from PVS1_VeryStrong to PVS1_Moderate per ClinGen SVI PVS1 recommendations.¹ This variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0 population databases (allele frequency = 0.0 in all datasets), meeting PM2 for extremely low population frequency.² Combining the above, two moderate-level pathogenic criteria (PVS1_Moderate + PM2_Moderate) are insufficient to reach a Likely Pathogenic classification under generic ACMG/AMP 2015 combination rules (PMID:25741868), which require at minimum one Very Strong plus one Moderate, one Strong plus one Moderate, or three Moderate criteria. No benign criteria are met. The variant is classified as a Variant of Uncertain Significance (VUS).³