NM_024675.4:c.928A>G (p.Ser310Gly) is a missense variant in PALB2, a gene in which primarily truncating variants are known to cause disease and missense pathogenic variation is not yet confirmed as a disease mechanism (VCEP v1.2.0).¹ The variant is present in gnomAD v4.1 at an overall allele frequency of 0.01276% (206/1,614,002 alleles, 0 homozygotes) with a grpmax filtering AF of 0.015106% in the European (non-Finnish) population. This exceeds the PALB2 VCEP BS1 threshold of >0.01%, supporting a benign interpretation at Strong strength.² SpliceAI predicts no significant splice impact (max delta score = 0.02), consistent with a missense change without cryptic splice effects.³ REVEL score is 0.034 and BayesDel score is -0.732, consistent with a benign in silico profile, though computational predictors have not been validated for PALB2 missense variant functional outcome per the VCEP.⁴ BP1 (Supporting) is applied per the PALB2 VCEP, which assigns this code to all missense variants given the very low prior probability that PALB2 missense variants are pathogenic.⁵ Combining BS1 (Strong benign) with BP1 (Supporting benign) yields a classification of Likely Benign per the ACMG/AMP combination rules adopted by the PALB2 VCEP (Rule 20: ≥1 Benign Strong criterion).⁶