PS1
Not assessed: insufficient evidence was available to evaluate this criterion.
PS2
Not assessed: no confirmed de novo observation (no parental testing or confirmation), so zero points under the VCEP de novo rule.
PS3
Not assessed: no VCEP-approved functional assay result (RAS/MEK/ERK activation) exists for this exact variant.
PS4
Not assessed: no case-control or proband-cohort enrichment data exists; the single gnomAD allele (AF 6.2e-07) provides no enrichment signal.
PM1
Not assessed: insufficient evidence was available to evaluate this criterion.
PM2
Not met: the variant is present in gnomAD v4.1 as a single South Asian exome allele (AF 6.2e-07), failing the VCEP absent-from-controls requirement.
PM4
Not met: the change is missense (p.Ile84Val) with no protein length change - the 189-amino-acid protein is unchanged.
PM5
Not assessed: insufficient evidence was available to evaluate this criterion.
PM6
Not assessed: no de novo occurrence is reported with or without parental confirmation, so the VCEP point rule cannot be scored.
PP1
Not assessed: no segregation data - zero informative meioses versus the >=3 required for Supporting.
PP2
Not assessed: insufficient evidence was available to evaluate this criterion.
PP3
Not met: REVEL 0.294 versus the VCEP >=0.7 threshold for missense variants.
PP5
Not met: no ClinVar expert-panel Pathogenic/Likely pathogenic classification exists - only two laboratory VUS submissions (GeneDx, Labcorp).
