PS1
Not assessed: no validated pathogenic same-amino-acid comparator for p.Gly413Asp was identified.
PS2
Not assessed: no confirmed de novo result or verified parental genotypes are documented for the proband's CBL p.Gly413Asp variant.
PS3
Not assessed: no variant-specific validated functional assay, controls, or biological readout were available for p.Gly413Asp.
PS4
Not assessed: no case-control counts or enrichment statistic for NM_005188.3:c.1238G>A were available.
PM1
Not assessed: no authoritative CBL domain boundary was available for residue 413, and no significant CBL G413 hotspot was found.
PM3
Not assessed: no affected-proband observation or phased pathogenic CBL variant in trans is documented for NM_005188.3:c.1238G>A.
PM5
Not assessed: zero eligible pathogenic or likely pathogenic same-residue comparator variants were identified at CBL residue 413.
PM6
Not assessed: no published or case-level evidence describes this CBL variant as de novo without parental confirmation.
PP1
Not assessed: zero affected relatives or informative meioses are documented for segregation of CBL c.1238G>A.
PP2
Not assessed: CBL loss-of-function evidence does not establish the missense-predominant disease mechanism and low benign missense variation required for PP2.
PP3
Not met: REVEL 0.628 is below the >=0.644 supporting PP3 threshold from the ClinGen SVI calibration.
PP4
Not assessed: no patient phenotype, family history, or disease-specific clinical description was available.
PP5
Not assessed: ClinVar has one exact-match laboratory Uncertain significance submission and zero expert-panel Pathogenic or Likely pathogenic assertions.
