I249L (p.Ile249Leu) variant of PSEN1 (Presenilin-1)
I249L (p.Ile249Leu) in PSEN1 (Presenilin-1) is a missense change. Clinical records from ClinVar, EBI, and UniProt describe it as pathogenic/likely pathogenic in the context of Alzheimer disease 3; Acne inversa, familial, 3; Frontotemporal dementia. The available variant effect predictions contribute to a CATVariant prioritization score of 0.67 / 1. The record also includes population frequency data, published literature, and structural context.
I249L (p.Ile249Leu) variant details
- p.Ile249Leu
- rs1362575880
- ClinGen CA390299857
- ClinVar RCV001289155
- ClinVar RCV001378264
- Pathogenic/Likely pathogenic
- Alzheimer disease 3; Acne inversa, familial, 3; Frontotemporal dementia
- Missense
- Variant Prioritization Score for Impact Estimate 0.667
- REVEL 0.77
- AlphaMissense 0.26
- MetaLR 0.96
- MetaSVM 1.03
- CADD 24.50
- PolyPhen-2 0.23
- ClinVar: Pathogenic/Likely pathogenic (Alzheimer disease 3; Acne inversa, familial, 3; Frontotemporal d)
- EBI: Pathogenic
- UniProt: Pathogenic
- Most common in the East Asian population (allele frequency 2.8e-05)
- Structural context available
- Cited in: EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. (PMID 20298421)
- Cited in: Alzheimer Disease Overview. (PMID 20301340)