PS1
Not met: the only p.Leu529Met functional report tested the index variant itself and found it functionally retained, with no independent same-amino-acid comparator.
PS2
Not assessed: no confirmed de novo observation or parental testing is documented for c.1585C>A.
PS3
Not met: p.Leu529Met was functionally retained in a MutY-deficient E.
PS4
Not assessed: no exact-variant affected-case count, control comparison, odds ratio, or enrichment threshold is available.
PM1
Not assessed: the applicable MUTYH specification provides no authoritative domain table or complete critical-domain boundaries for checking residue 529.
PM2
Not met: non-cancer gnomAD frequencies of 0.00363 and 0.00155 exceed the generic PM2 threshold of 0.0001.
PM3
Not assessed: no affected-proband observation or validated pathogenic MUTYH allele in trans is documented for this autosomal-recessive condition.
PM5
Not assessed: no independent pathogenic or likely pathogenic missense comparator at MUTYH residue 529 was identified for p.Leu529Met.
PM6
Not assessed: no apparently de novo proband report without parental testing is documented for c.1585C>A.
PP1
Not assessed: zero informative family members or meioses are documented for segregation of c.1585C>A.
PP2
Not met: MUTYH has numerous missense variants and established recurrent missense disease variants, so the PP2 low-benign-missense pattern is not demonstrated.
PP3
Not met: REVEL 0.237 is below the >=0.644 supporting PP3 threshold for missense variants.
PP4
Not assessed: no exact-variant patient phenotype or phenotype-specific diagnostic context is available for PP4.
PP5
Not met: ClinVar records 0 expert-panel submissions, and the available exact-variant submissions are Benign or Likely benign.
