Alzheimer disease: genes and variants
Explore variant evidence for Alzheimer disease across 33 analyzed proteins (PSEN1, APP, PSEN2, CSF1R, MAPT and 28 more). Linked ClinVar records include 120 pathogenic or likely pathogenic variants, 273 variants of uncertain significance and 59 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-01. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Alzheimer disease
PSEN1: Presenilin-1
Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.
88 ClinVar pathogenic / likely pathogenic and 72 uncertain variants in PSEN1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
APP: Amyloid-beta precursor protein
Its processing produces multiple fragments involved in neuronal biology, including amyloid-beta peptides generated by beta- and gamma-secretase cleavage. Increased amyloidogenic processing, pathogenic variants, or increased gene dosage can cause autosomal dominant Alzheimer disease or cerebral amyloid angiopathy.
22 ClinVar pathogenic / likely pathogenic and 154 uncertain variants in APP have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
PSEN2: Presenilin-2
Its gamma-secretase activity contributes to intramembrane cleavage of APP and other substrates in endolysosomal and cellular membranes. Pathogenic variants are a rare cause of autosomal dominant Alzheimer disease, generally with more variable penetrance and age of onset than PSEN1 variants.
5 ClinVar pathogenic / likely pathogenic and 87 uncertain variants in PSEN2 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CSF1R: Macrophage colony-stimulating factor 1 receptor
Signals from CSF1 and IL-34 through this pathway are required for development, survival, and function of macrophages and microglia. Pathogenic variants can cause adult-onset leukoencephalopathy with cognitive, psychiatric, and motor deterioration.
2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CSF1R have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
MAPT: Microtubule-associated protein tau
Its tau isoforms stabilize and organize neuronal microtubules, especially in axons, while also participating in transport and signaling. Pathogenic variants cause inherited frontotemporal dementia, and abnormal tau aggregation defines multiple neurodegenerative tauopathies.
2 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MAPT have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
VCP: Transitional endoplasmic reticulum ATPase
It uses ATP to extract ubiquitinated proteins from complexes or membranes for recycling or degradation and is central to proteostasis, ER-associated degradation, and autophagy. Dominant pathogenic variants cause multisystem proteinopathy with inclusion-body myopathy, Paget disease, frontotemporal dementia, or ALS.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in VCP have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
APOE: Apolipoprotein E
It redistributes cholesterol and other lipids between tissues by directing remnant lipoproteins to LDL-receptor-family members. The common epsilon4 isoform strongly increases late-onset Alzheimer disease risk and also influences plasma lipids and cardiovascular risk.
0 ClinVar pathogenic / likely pathogenic and 13 uncertain variants in APOE have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
HFE: Hereditary hemochromatosis protein
It helps the liver sense circulating iron availability and regulate hepcidin, thereby controlling intestinal iron absorption and systemic iron distribution. The C282Y variant is the major genetic cause of HFE-related hereditary hemochromatosis and progressive iron overload.
0 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in HFE have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
SORL1: Sortilin-related receptor
It sorts APP and other cargo between endosomes, Golgi, and the cell surface, helping keep APP away from amyloidogenic processing compartments. Rare loss-of-function variants and common variation can substantially increase Alzheimer disease risk.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SORL1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
ACE: Angiotensin-converting enzyme
A membrane-associated enzyme that removes terminal dipeptides from hormones and signaling peptides, including angiotensin I and bradykinin. By generating angiotensin II and inactivating vasodilators, it helps regulate blood pressure, fluid balance, and aspects of nervous-system signaling.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ACE have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
ATP6V1A: V-type proton ATPase catalytic subunit A
It provides ATP-hydrolyzing activity to the vacuolar proton pump, driving acidification of endosomes, lysosomes, and secretory vesicles. De novo pathogenic variants can cause developmental encephalopathy with epilepsy and intellectual disability.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ATP6V1A have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
AURKA: Aurora kinase A
It coordinates centrosome maturation, spindle assembly, and chromosome segregation during mitosis. Overexpression or amplification can promote chromosomal instability and tumor progression, making its kinase activity a target of anticancer drug development.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in AURKA have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
AURKB: Aurora kinase B
It controls chromosome alignment, kinetochore-microtubule attachment, the spindle checkpoint, and cytokinesis as part of the chromosomal passenger complex. Excess activity is common in proliferative cancers and can contribute to aneuploidy and treatment resistance.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in AURKB have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
AXL: Tyrosine-protein kinase receptor UFO
Activation by GAS6 promotes cell survival, migration, immune modulation, and resistance to cellular stress. Persistent signaling is common in advanced cancers and can support epithelial-to-mesenchymal transition, metastasis, and resistance to targeted or immune therapies.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in AXL have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
BIN1: Myc box-dependent-interacting protein 1
It shapes cellular membranes and participates in endocytosis, T-tubule organization in muscle, and membrane trafficking in neurons. Pathogenic variants can cause centronuclear myopathy, while common variation at the BIN1 locus is strongly associated with late-onset Alzheimer disease risk.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in BIN1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CDK1: Cyclin-dependent kinase 1
It is the central kinase that drives cells into mitosis and coordinates chromosome condensation, nuclear-envelope breakdown, spindle assembly, and other mitotic events. Because proliferating tumor cells depend on tightly regulated CDK1 activity, its pathway is extensively studied as an anticancer target.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDK1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CDK12: Cyclin-dependent kinase 12
It promotes transcription of long DNA-repair and genome-maintenance genes through RNA-polymerase-II phosphorylation. Loss-of-function alterations occur in prostate, ovarian, and other cancers and can create a characteristic pattern of genomic instability.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDK12 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CDK4: Cyclin-dependent kinase 4
Together with D-type cyclins, it phosphorylates RB-family proteins and commits cells to progress from G1 toward DNA replication. Amplification or pathway activation is common in cancer, while rare activating germline variants predispose to familial melanoma.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDK4 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CDKN1C: Cyclin-dependent kinase inhibitor 1C
It restrains embryonic and placental cell proliferation and is subject to parent-of-origin-specific genomic imprinting. Loss of maternal expression contributes to Beckwith-Wiedemann syndrome, whereas gain-of-function variants can cause growth-restriction syndromes such as IMAGe syndrome.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDKN1C have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CDKN2A: Tumor suppressor ARF
The ARF product of CDKN2A is a tumor-suppressor protein that binds MDM2 and helps preserve p53 activity. By promoting cell-cycle arrest and apoptosis, it provides an important barrier to uncontrolled cell growth from within the nucleolus.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CDKN2A have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CLU: Clusterin
It acts as an extracellular chaperone and participates in lipid transport, complement regulation, apoptotic-cell clearance, and responses to tissue injury. Common variation near CLU influences late-onset Alzheimer disease risk, and altered expression is observed in cardiovascular disease and cancer.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CLU have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
CR1: Complement receptor type 1
It binds C3b and C4b, promotes clearance of complement-coated immune complexes, and helps restrain complement activation on cell surfaces. Copy-number and sequence variation can influence complement biology and has been associated with diseases including Alzheimer disease and malaria-related phenotypes.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in CR1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
FOXO3: Forkhead box protein O3
It activates stress-resistance, autophagy, cell-cycle arrest, and apoptotic programs when growth-factor signaling is low. Variation near FOXO3 has repeatedly been associated with human longevity, while altered activity influences cancer and metabolic disease.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in FOXO3 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
GRIN2A: Glutamate receptor ionotropic, NMDA 2A
It helps determine the kinetics and signaling properties of NMDA receptors, particularly in cortical circuits involved in language and epilepsy. Pathogenic variants cause a spectrum of developmental epileptic encephalopathies and epilepsy-aphasia disorders.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN2A have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
GRIN2B: Glutamate receptor ionotropic, NMDA 2B
It confers distinct developmental and signaling properties on NMDA receptors and is highly expressed during early brain development. De novo pathogenic variants can cause intellectual disability, developmental delay, epilepsy, abnormal movements, and autism-related phenotypes.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRIN2B have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
GRN: Progranulin
It is secreted and proteolytically processed into granulins and has roles in lysosomal function, inflammation, neuronal survival, and tissue repair. Heterozygous loss-of-function variants cause frontotemporal dementia through progranulin haploinsufficiency, while biallelic loss causes neuronal ceroid lipofuscinosis.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in GRN have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
HMGCR: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
It controls the rate-limiting step of the mevalonate pathway and therefore strongly regulates endogenous cholesterol production. Statins lower LDL cholesterol by inhibiting this activity, causing the liver to increase LDL-receptor-mediated clearance from blood.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in HMGCR have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
NAT1: Arylamine N-acetyltransferase 1
It acetylates aromatic amines and related xenobiotics and participates in metabolism of selected endogenous substrates. Genetic variation can alter activity and exposure to some chemicals, although clinical pharmacogenomic effects are generally less established than for NAT2.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in NAT1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
PLCG2: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
It generates IP3 and diacylglycerol downstream of immune receptors, triggering intracellular calcium release and protein-kinase-C signaling in B cells and myeloid cells. Gain-of-function variants cause autoinflammatory and antibody-deficiency syndromes, while somatic mutations can mediate resistance to BTK inhibitors.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PLCG2 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
PLK1: Serine/threonine-protein kinase PLK1
It coordinates centrosome maturation, chromosome segregation, spindle function, and cytokinesis during mitosis. Many tumors overexpress PLK1 and depend on its activity for rapid proliferation, making it a prominent anticancer drug target.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in PLK1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
SLC18A2: Synaptic vesicular amine transporter
It packages dopamine, serotonin, norepinephrine, and other monoamines into acidic secretory vesicles for regulated release. Biallelic loss-of-function variants cause a severe monoamine neurotransmitter disorder, while pharmacologic inhibition is used to treat hyperkinetic movement disorders.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SLC18A2 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
SLC6A3: Sodium-dependent dopamine transporter
It clears dopamine from the synaptic cleft back into presynaptic neurons and thereby controls the duration and intensity of dopamine signaling. Biallelic pathogenic variants cause dopamine-transporter deficiency syndrome with early dystonia and progressive parkinsonism.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SLC6A3 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
SMPD1: Sphingomyelin phosphodiesterase
It hydrolyzes sphingomyelin to ceramide in lysosomes and participates in membrane-lipid turnover and stress signaling. Biallelic loss-of-function variants cause acid sphingomyelinase deficiency, including Niemann-Pick disease types A and B.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in SMPD1 have source records linked to Alzheimer disease. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): NOS3 and PLAU.
Where Alzheimer disease variants cluster
- APP Transmembrane (positions 702–722): 10 of 22 ClinVar pathogenic / likely pathogenic variants, 16.7× more than its size predicts.
- PSEN1 Transmembrane (positions 249–272): 14 of 88 ClinVar pathogenic / likely pathogenic variants, 3.1× more than its size predicts.
- PSEN1 Transmembrane (positions 133–153): 10 of 88 ClinVar pathogenic / likely pathogenic variants, 2.5× more than its size predicts.
- PSEN1 Important for cleavage of target proteins (positions 377–381): 3 of 88 ClinVar pathogenic / likely pathogenic variants, 3.2× more than its size predicts.
- PSEN1 Transmembrane (positions 83–103): 6 of 88 ClinVar pathogenic / likely pathogenic variants, 1.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Alzheimer disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| APP V717I | 717 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M146L | 146 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 P267T | 267 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 P267L | 267 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 R269H | 269 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 E280G | 280 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| APP V717F | 717 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 T116N | 116 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 P117L | 117 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 M139K | 139 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M139T | 139 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M139V | 139 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 I143T | 143 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M146I | 146 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M233T | 233 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M233V | 233 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 I249L | 249 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 R269G | 269 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L392V | 392 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A431E | 431 | Required for interaction with CTNNB1 | Pathogenic / likely pathogenic (★★) |
| PSEN1 A431V | 431 | Required for interaction with CTNNB1 | Pathogenic / likely pathogenic (★★) |
| APP E674Q | 674 | Extracellular | Pathogenic / likely pathogenic (★★) |
| APP E693Q | 693 | Extracellular | Pathogenic / likely pathogenic (★★) |
| APP A713T | 713 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| APP I716V | 716 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A79V | 79 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 T119I | 119 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 A246E | 246 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 L262F | 262 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 P264L | 264 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| APP D694N | 694 | Extracellular | Pathogenic / likely pathogenic (★★) |
| APP T714A | 714 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| APP I716F | 716 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L85P | 85 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L113P | 113 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 Y115C | 115 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 N135S | 135 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 S169L | 169 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 G206D | 206 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 S212Y | 212 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A231T | 231 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L271V | 271 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L381F | 381 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L418F | 418 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| APP V715M | 715 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 C92S | 92 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 F177S | 177 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 G217R | 217 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 A285V | 285 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 A426P | 426 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN2 N141I | 141 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 I416T | 416 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 H163R | 163 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| APP T714I | 714 | Transmembrane | Pathogenic / likely pathogenic (★) |
| APP I716T | 716 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 M84V | 84 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 T116I | 116 | Lumenal | Pathogenic / likely pathogenic (★) |
| PSEN1 P117S | 117 | Lumenal | Pathogenic / likely pathogenic (★) |
| PSEN1 I143V | 143 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 G209E | 209 | Transmembrane | Pathogenic / likely pathogenic (★) |
Showing 60 of 120.
Uncertain variants prioritized for review in Alzheimer disease
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PSEN1 A260G | 260 | Transmembrane | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; A260V at the same position is pathogenic; REVEL 0.966 |
| APP A713V | 713 | Transmembrane | Conflicting reports (★) | +6: 7 other pathogenic changes within 3 positions; A713T at the same position is pathogenic; REVEL 0.928 |
| PSEN1 A79T | 79 | Cytoplasmic | Uncertain (★) | +6: in a 3D region that tolerates change poorly (1R); A79V at the same position is pathogenic; REVEL 0.969 |
| PSEN1 F86L | 86 | Transmembrane | Uncertain (★) | +6: 4 other pathogenic changes within 3 positions; F86C at the same position is pathogenic; REVEL 0.816 |
Which prediction tools work for Alzheimer disease
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MetaLR: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 94 out of 100
- EVE: 92 out of 100
- MutPred2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 85 out of 100
- SIFT: 84 out of 100
- phyloP: 78 out of 100
Same protein, different disease
- Pick disease also has ClinVar records linked to PSEN1 variants; they fall in the same places as the Alzheimer disease variants (26 pathogenic / likely pathogenic).
- Leukoencephalopathy, diffuse hereditary, with spheroids 1 also has ClinVar records linked to CSF1R variants; they fall mostly in different places as the Alzheimer disease variants (13 pathogenic / likely pathogenic).
- Hereditary diffuse leukoencephalopathy with spheroids also has ClinVar records linked to CSF1R variants; they fall mostly in different places as the Alzheimer disease variants (9 pathogenic / likely pathogenic).
- Frontotemporal dementia also has ClinVar records linked to MAPT variants; they fall mostly in different places as the Alzheimer disease variants (17 pathogenic / likely pathogenic).
- Supranuclear palsy, progressive, 1 also has ClinVar records linked to MAPT variants; they fall mostly in different places as the Alzheimer disease variants (6 pathogenic / likely pathogenic).
- Pick disease also has ClinVar records linked to MAPT variants; they fall mostly in different places as the Alzheimer disease variants (5 pathogenic / likely pathogenic).
- Inclusion body myopathy with Paget disease of bone and frontotemporal dementia also has ClinVar records linked to VCP variants; they fall mostly in different places as the Alzheimer disease variants (31 pathogenic / likely pathogenic).
- Frontotemporal dementia and/or amyotrophic lateral sclerosis also has ClinVar records linked to VCP variants; they fall mostly in different places as the Alzheimer disease variants (30 pathogenic / likely pathogenic).
- Childhood Onset VCP-related Neurodevelopmental Disorder also has ClinVar records linked to VCP variants; they fall mostly in different places as the Alzheimer disease variants (4 pathogenic / likely pathogenic).
Diseases related to Alzheimer disease
- Parkinson disease, also linked to AURKA, AURKB, AXL, CDK1 and 11 more
- Dementia, also linked to APOE, APP, GRIN2A, GRIN2B and 2 more
- Frontotemporal dementia, also linked to GRN, MAPT and PSEN1
- Type 2 diabetes mellitus, also linked to ACE, APOE and HMGCR
- Myocardial infarction, also linked to ACE, APOE and HMGCR
- Early-onset autosomal dominant Alzheimer disease, also linked to APOE, PSEN1 and PSEN2
- Familial hypercholesterolemia, also linked to APOE and HMGCR
- Dilated cardiomyopathy, also linked to PSEN1 and PSEN2
- Hyperlipoproteinemia, also linked to APOE and HMGCR
- Pick disease, also linked to MAPT and PSEN1
- Epilepsy, also linked to GRIN2A and GRIN2B
- Familial melanoma, also linked to CDK4 and CDKN2A
Frequently asked questions
Which genes have records linked to Alzheimer disease?
This view contains 33 analyzed proteins: PSEN1, APP, PSEN2, CSF1R, MAPT and 28 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 120 pathogenic or likely pathogenic variants, 273 variants of uncertain significance and 59 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 4 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 549 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center