PS1
Not met: no different-nucleotide change producing p.Ala174Thr with a pathogenic assertion exists in ClinVar or the literature.
PS2
Not assessed: no proband-parent trio or parental testing data were available to evaluate a de novo origin.
PS3
Not assessed: no functional studies of this variant (enzyme, cellular, or animal assays) were available.
PS4
Not met: no case-control enrichment evidence exists; the variant is essentially absent from population controls (gnomAD AF 6.2e-07).
PM1
Not met: residue 174 is not a hotspot; IDH2's established hotspots are catalytic residues R140 and R172.
PM3
Not met: no observation of this variant in trans with a pathogenic IDH2 variant was available.
PM5
Not assessed: no pathogenic alternate missense at residue 174 was identified, so a different-missense comparator could not be confirmed.
PM6
Not assessed: no de novo occurrence or parental testing is documented for this variant.
PP1
Not assessed: no family segregation or pedigree data were available.
PP2
Not assessed: no gene-level missense constraint metric (gnomAD Z-score) was available to evaluate PP2.
PP3
Not met: REVEL 0.749 is below the calibrated 0.773 PP3-supporting threshold.
PP4
Not assessed: no proband phenotype or family history data were available to evaluate phenotype specificity.
PP5
Not met: ClinVar holds only a single-submitter laboratory VUS, with no expert-panel pathogenic classification.
