The RUNX1 c.1332_1334delinsG (p.Leu445GlyfsTer127) variant has been reported in ClinVar, including a Likely Pathogenic expert-panel classification by the ClinGen Myeloid Malignancy VCEP.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, so the observed population frequency is 0 and is below the RUNX1 PM2_Supporting threshold of 0.00005.² This is a RUNX1 frameshift variant in a gene with an established loss-of-function disease mechanism, supporting use of the RUNX1 PVS1 framework, although the distal position suggests a downgraded rather than full very-strong PVS1 strength.³ SpliceAI predicts no significant splice impact for this variant, with a max delta score of 0.00, which supports the RUNX1 PM5_Supporting rule for downstream nonsense or frameshift variants and does not support PP3 or BP4 application for this frameshift event.⁴