PVS1
Not met: c.454+23C>T is deep intronic with a SpliceAI delta of 0.008, not a canonical splice or null variant.
PS2
Not assessed: no parental testing was available to confirm the variant arose de novo in this individual.
PS3
Not assessed: no RNA, minigene, or protein assay was performed, and a SpliceAI prediction of 0.008 is computational only.
PS4
Not assessed: no case-control or affected-count data were available to test for enrichment in disease.
PM2
Not met: gnomAD v4.1 frequency reaches 0.525% in African/African American individuals, above the <0.1% PM2 rarity threshold.
PM3
Not assessed: no phase data or co-occurring pathogenic variant in trans were available to evaluate this recessive criterion.
PM4
Not met: this single-nucleotide intronic substitution does not change protein length, unlike in-frame indels or stop-loss variants.
PM6
Not assessed: no parental testing or family data were available to support a de novo occurrence.
PP1
Not assessed: no family pedigree or relative genotype data were available to evaluate cosegregation with disease.
PP3
Not met: SpliceAI maximum delta 0.008 falls well below the >0.2 PP3 threshold for predicted splice impact.
PP4
Not assessed: no proband phenotype or clinical diagnosis was supplied to assess phenotype specificity to SMAD4.
PP5
Not met: the ClinVar record is a single-submitter Likely benign assertion with no expert-panel review.
