APP (Amyloid-beta precursor protein) variants and mutations
APP (also known as Amyloid-beta precursor protein) is a human protein-coding gene encoding an 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. This analysis covers 1,078 APP variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes Alzheimer disease, Alzheimer disease type 1, and cerebral amyloid angiopathy, APP-related. Example APP variants include P3H, L5F, and L5V.
Variant analysis overview
- Gene: APP
- Protein: Amyloid-beta precursor protein
- UniProt accession: P05067
- Organism: Homo sapiens
- Variants analyzed: 1078
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 882 unspecified-consequence records; 97 synonymous variants; 78 missense variants; 8 in-frame deletions; 6 splice-region variants; 2 stop-gained variants; 3 frameshift variants; 2 in-frame insertions
- Prediction scores: 819 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Alzheimer disease, Alzheimer disease type 1, cerebral amyloid angiopathy, APP-related, dementia, Hereditary cerebral hemorrhage with amyloidosis, Piedmont type, Hereditary cerebral hemorrhage with amyloidosis, Dutch type, Hereditary cerebral hemorrhage with amyloidosis, Italian type, Hereditary cerebral hemorrhage with amyloidosis, Iowa type, Hereditary cerebral hemorrhage with amyloidosis, Arctic type, Hereditary cerebral hemorrhage with amyloidosis, Flemish type, Hereditary cerebral hemorrhage with amyloidosis, Cognitive impairment.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 3 domains; 15 binding sites; 21 post-translational modification sites.
- Structural context: 496 variants have structural context.
- PTM context: 34 variants overlap post-translational modification sites.
- Experimental data: 42 protein positions have experimental scores. Source: Amino acid scores for Aβ42 variants, Single amino acid substitutions.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, LitVar, MaveDB.
Diseases linked to APP
Notable APP variants
Examples include P3H, L5F, L5V, A6V, L7V, L8F, A11S, A11T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P3H (p.Pro3His), TOPMed rs2063726231, REVEL 0.35, CADD 24.30
- L5F (p.Leu5Phe), rs2517491839, ClinGen CA410167266, ClinVar RCV003881635, REVEL 0.16, CADD 20.70, Uncertain significance, Alzheimer disease
- L5V (p.Leu5Val), rs1446208112, ClinGen CA410167270, ClinVar RCV003288229, ClinVar RCV005102651, REVEL 0.13, CADD 15.20, Uncertain significance, Alzheimer disease; Inborn genetic diseases
- A6V (p.Ala6Val), gnomAD rs2063726028, REVEL 0.11, CADD 21.00
- L7V (p.Leu7Val), rs767211549, ClinGen CA9987780, ClinVar RCV001878421, ExAC rs767211549, REVEL 0.30, CADD 21.20, Likely benign, Alzheimer disease
- L8F (p.Leu8Phe), TOPMed rs1712579057, REVEL 0.23, CADD 21.60
- A11S (p.Ala11Ser), NCI-TCGA TCGA novel, REVEL 0.21, CADD 20.40, Variant assessed as somatic; moderate impact.
- A11T (p.Ala11Thr), rs1180882911, 1000Genomes rs1180882911, gnomAD rs1180882911, REVEL 0.17, CADD 22.20, Variant assessed as somatic; moderate impact.
- A12T (p.Ala12Thr), gnomAD rs2063725474, REVEL 0.20, CADD 22.10
- A12V (p.Ala12Val), Ensembl rs1601618931, REVEL 0.15, CADD 21.70
- W13* (p.Trp13Ter), Ensembl rs1569061063, CADD 39.00
- W13R (p.Trp13Arg), TOPMed rs1206506558, gnomAD rs1206506558, REVEL 0.41, CADD 23.40
- A15G (p.Ala15Gly), 1000Genomes rs913925398, TOPMed rs913925398, gnomAD rs913925398, Likely benign
- A15V (p.Ala15Val), rs913925398, ClinGen CA410167207, ClinVar RCV001425635, 1000Genomes rs913925398, REVEL 0.25, CADD 22.50, Likely benign, Alzheimer disease
- R16P (p.Arg16Pro), TOPMed rs955517095, gnomAD rs955517095, REVEL 0.53, CADD 22.60, Uncertain significance, Alzheimer disease
- R16Q (p.Arg16Gln), rs955517095, ClinGen CA319572175, ClinVar RCV001136836, ClinVar RCV001355941, REVEL 0.24, CADD 21.80, Uncertain significance, Cerebral amyloid angiopathy, APP-related; Alzheimer disease type 1; Alzheimer di
- R16W (p.Arg16Trp), rs202070273, ClinGen CA9987777, ClinVar RCV001341603, ClinVar RCV004746330, REVEL 0.42, CADD 24.80, Uncertain significance, not provided; Alzheimer disease
- A17S (p.Ala17Ser), ExAC rs762505107, TOPMed rs762505107, gnomAD rs762505107, REVEL 0.30, CADD 22.80
- A17T (p.Ala17Thr), ExAC rs762505107, TOPMed rs762505107, gnomAD rs762505107, REVEL 0.47, CADD 24.30
- E19K (p.Glu19Lys), rs1375631745, TOPMed rs1375631745, gnomAD rs1375631745, REVEL 0.62, CADD 24.10, Variant assessed as somatic; moderate impact.
- E19V (p.Glu19Val), TOPMed rs1280139639, gnomAD rs1280139639, REVEL 0.62, CADD 29.80
- V20I (p.Val20Ile), ESP rs140350218, ExAC rs140350218, gnomAD rs140350218, REVEL 0.38, CADD 23.10, Benign/Likely benign, not specified; Alzheimer disease
- P21S (p.Pro21Ser), TOPMed rs1482948530, gnomAD rs1482948530, REVEL 0.44, CADD 22.40
- T22A (p.Thr22Ala), ExAC rs761648158, TOPMed rs761648158, gnomAD rs761648158, REVEL 0.24, CADD 17.90
- T22S (p.Thr22Ser), ExAC rs761648158, TOPMed rs761648158, gnomAD rs761648158, REVEL 0.40, CADD 21.00
- D23A (p.Asp23Ala), TOPMed rs1568989344, gnomAD rs1568989344, REVEL 0.53, CADD 25.10
- D23N (p.Asp23Asn), gnomAD rs1297968881, REVEL 0.39, CADD 24.00
- N25I (p.Asn25Ile), TOPMed rs2062339570, gnomAD rs2062339570, REVEL 0.62, CADD 22.90
- A26G (p.Ala26Gly), ExAC rs763852444, gnomAD rs763852444, REVEL 0.43, CADD 23.80
- A26V (p.Ala26Val), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- A30G (p.Ala30Gly), Ensembl rs55979514
- E31D (p.Glu31Asp), rs1568989313, ClinGen CA410167100, ClinVar RCV002929455, Ensembl rs1568989313, AlphaMissense 0.81, MetaLR 0.91, Uncertain significance, Inborn genetic diseases
- P32A (p.Pro32Ala), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- P32L (p.Pro32Leu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- I34N (p.Ile34Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I34V (p.Ile34Val), Ensembl rs1601492248, REVEL 0.17, CADD 15.00, Uncertain significance, Alzheimer disease
- A35V (p.Ala35Val), TOPMed rs1415572087
- G39V (p.Gly39Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R40K (p.Arg40Lys), ExAC rs772213572, gnomAD rs772213572, REVEL 0.32, CADD 17.30
- L41M (p.Leu41Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L41V (p.Leu41Val), rs886056997, ClinGen CA10650338, ClinVar RCV000407575, Ensembl rs886056997, REVEL 0.81, CADD 26.30, Uncertain significance, Alzheimer disease
- N42H (p.Asn42His), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- M43V (p.Met43Val), TOPMed rs2062338414, REVEL 0.89, CADD 25.30, Uncertain significance, Alzheimer disease type 1
- H44Y (p.His44Tyr), rs774281569, ClinGen CA9987747, ClinVar RCV002005546, ExAC rs774281569, REVEL 0.94, CADD 27.40, Uncertain significance, Alzheimer disease
- M45I (p.Met45Ile), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- M45L (p.Met45Leu), ExAC rs771509390, gnomAD rs771509390, REVEL 0.40, CADD 22.30
- M45R (p.Met45Arg), TOPMed rs1462998749
- Q48H (p.Gln48His), gnomAD rs2062337896, REVEL 0.79, CADD 24.70
- Q48R (p.Gln48Arg), TOPMed rs1387322785, REVEL 0.81, CADD 24.70
- N49D (p.Asn49Asp), gnomAD rs2062337831, REVEL 0.54, CADD 24.50
- N49S (p.Asn49Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K51N (p.Lys51Asn), 1000Genomes rs529782627, ExAC rs529782627, gnomAD rs529782627, REVEL 0.74, CADD 23.90
- K51R (p.Lys51Arg), ExAC rs749737592, gnomAD rs749737592, REVEL 0.58, CADD 24.60
- S54L (p.Ser54Leu), Ensembl rs56111408
- D55Y (p.Asp55Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G58V (p.Gly58Val), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- T59I (p.Thr59Ile), ExAC rs779869655, TOPMed rs779869655, gnomAD rs779869655, Uncertain significance, Alzheimer disease
- T61I (p.Thr61Ile), gnomAD rs11549661
- T61S (p.Thr61Ser), gnomAD rs11549661, REVEL 0.40, CADD 17.10
- C62Y (p.Cys62Tyr), rs2146206105, ClinGen CA410166887, ClinVar RCV002224581, Ensembl rs2146206105, AlphaMissense 0.97, MetaLR 0.98, Uncertain significance, not provided
- I63M (p.Ile63Met), TOPMed rs1339370778, gnomAD rs1339370778
- I63T (p.Ile63Thr), gnomAD rs200648330, REVEL 0.82, CADD 25.10
- I63V (p.Ile63Val), rs779329120, ClinGen CA319565274, ClinVar RCV003402157, TOPMed rs779329120, AlphaMissense 0.08, MetaLR 0.70, Uncertain significance, APP-related disorder
- D64A (p.Asp64Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K66E (p.Lys66Glu), ExAC rs778250646, gnomAD rs778250646, REVEL 0.90, CADD 27.30
- K66N (p.Lys66Asn), TOPMed rs1411114284, gnomAD rs1411114284, REVEL 0.78, CADD 24.60
- K66R (p.Lys66Arg), TOPMed rs1358123055, gnomAD rs1358123055, REVEL 0.82, CADD 27.80
- E67G (p.Glu67Gly), TOPMed rs1351702564, gnomAD rs1351702564, REVEL 0.91, CADD 31.00, Uncertain significance, Inborn genetic diseases
- E67K (p.Glu67Lys), Ensembl rs1601491869
- G68A (p.Gly68Ala), TOPMed rs1307925400, gnomAD rs1307925400, REVEL 0.65, CADD 22.80, Uncertain significance, Inborn genetic diseases
- G68D (p.Gly68Asp), cosmic curated COSV61001, TOPMed rs1307925400, gnomAD rs1307925400, REVEL 0.34, CADD 20.90
- I69V (p.Ile69Val), rs1428253800, ClinGen CA410166841, ClinVar RCV002914426, TOPMed rs1428253800, REVEL 0.49, CADD 19.50, Uncertain significance, Alzheimer disease
- Q71R (p.Gln71Arg), ExAC rs757264249, TOPMed rs757264249, gnomAD rs757264249, REVEL 0.67, CADD 24.10
- C73Y (p.Cys73Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q74L (p.Gln74Leu), ExAC rs753737986, REVEL 0.93, CADD 32.00
- V76A (p.Val76Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V76I (p.Val76Ile), rs151188448, ClinGen CA9987709, ClinVar RCV001664518, ClinVar RCV002064847, REVEL 0.51, CADD 25.20, Benign/Likely benign, not specified; Alzheimer disease
- V76L (p.Val76Leu), ESP rs151188448, ExAC rs151188448, TOPMed rs151188448, gnomAD rs151188448, REVEL 0.73, CADD 32.00, Benign
- P78A (p.Pro78Ala), ExAC rs770493889, TOPMed rs770493889, gnomAD rs770493889
- P78S (p.Pro78Ser), ExAC rs770493889, TOPMed rs770493889, gnomAD rs770493889, REVEL 0.81, CADD 23.50
- P78T (p.Pro78Thr), ExAC rs770493889, TOPMed rs770493889, gnomAD rs770493889, REVEL 0.93, CADD 23.40
- N84S (p.Asn84Ser), ExAC rs777179682, TOPMed rs777179682, gnomAD rs777179682, REVEL 0.82, CADD 26.50, Uncertain significance, Alzheimer disease
- V86A (p.Val86Ala), NCI-TCGA TCGA novel, REVEL 0.72, CADD 25.40, Variant assessed as somatic; moderate impact.
- V86I (p.Val86Ile), ExAC rs768921158, gnomAD rs768921158, REVEL 0.74, CADD 25.50
- P91Q (p.Pro91Gln), rs1394215533, ClinGen CA409862648, ClinVar RCV003988314, TOPMed rs1394215533, REVEL 0.90, CADD 28.80, Uncertain significance, not specified
- P91S (p.Pro91Ser), ExAC rs747355134, gnomAD rs747355134
- I94V (p.Ile94Val), TOPMed rs1393106190
- Q95E (p.Gln95Glu), rs950592627, ClinGen CA319562680, ClinVar RCV000516620, ClinVar RCV001857895, REVEL 0.37, CADD 18.80, Uncertain significance, not specified; Alzheimer disease
- N96I (p.Asn96Ile), gnomAD rs1404320222, REVEL 0.91, CADD 28.00
- K99R (p.Lys99Arg), TOPMed rs2061789341, REVEL 0.53, CADD 24.10, Likely benign, Alzheimer disease
- R100P (p.Arg100Pro), 1000Genomes rs199741007, ExAC rs199741007, TOPMed rs199741007, gnomAD rs199741007, REVEL 0.64, CADD 25.70
- R100Q (p.Arg100Gln), cosmic curated COSV61006, 1000Genomes rs199741007, ExAC rs199741007, TOPMed rs199741007, REVEL 0.46, CADD 23.70
- R100W (p.Arg100Trp), rs200347552, ClinGen CA9987702, cosmic curated COSV61005, ClinVar RCV000813633, REVEL 0.73, CADD 26.30, Uncertain significance, Alzheimer disease
- G101C (p.Gly101Cys), Ensembl rs1555873562
- G101D (p.Gly101Asp), rs532382285, ClinGen CA9987700, NCI-TCGA Cosmic COSV1006, ClinVar RCV001302188, REVEL 0.61, AlphaMissense 0.24, Likely benign, Alzheimer disease
- G101V (p.Gly101Val), rs532382285, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, 1000Genomes rs532382285, AlphaMissense 0.24, MetaLR 0.92, Likely benign
- R102H (p.Arg102His), rs777260127, ClinGen CA9987699, ClinVar RCV003509237, ExAC rs777260127, REVEL 0.69, CADD 26.10, Likely benign, Alzheimer disease
- Q104R (p.Gln104Arg), gnomAD rs1449764914, REVEL 0.70, CADD 24.10
- K106N (p.Lys106Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H110Q (p.His110Gln), TOPMed rs202145222, gnomAD rs202145222, REVEL 0.81, CADD 23.80
- V112A (p.Val112Ala), NCI-TCGA TCGA novel, REVEL 0.92, CADD 26.20, Variant assessed as somatic; moderate impact.
- P114S (p.Pro114Ser), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61002, Variant assessed as somatic; moderate impact.
- Y115H (p.Tyr115His), Ensembl rs1601431721
- R116C (p.Arg116Cys), cosmic curated COSV10648, TOPMed rs2061787807, REVEL 0.85, CADD 32.00
- R116H (p.Arg116His), rs2061787725, ClinGen CA409862478, ClinVar RCV001288438, ClinVar RCV003509666, REVEL 0.75, CADD 25.10, Uncertain significance, Alzheimer disease; not provided
- L118V (p.Leu118Val), Ensembl rs2061787551
- V119F (p.Val119Phe), ExAC rs754736666, TOPMed rs754736666, REVEL 0.84, CADD 33.00
- G120A (p.Gly120Ala), ExAC rs759854517, gnomAD rs759854517, REVEL 0.92, CADD 26.30
- S124N (p.Ser124Asn), NCI-TCGA TCGA novel, REVEL 0.77, CADD 26.40, Variant assessed as somatic; moderate impact.
- D125N (p.Asp125Asn), TOPMed rs1386906450, gnomAD rs1386906450, REVEL 0.77, CADD 32.00
- A126T (p.Ala126Thr), gnomAD rs1183474845, REVEL 0.89, CADD 28.30
- L127I (p.Leu127Ile), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- L128V (p.Leu128Val), gnomAD rs2045912264, REVEL 0.83, CADD 26.30
- V129F (p.Val129Phe), ExAC rs563647959, gnomAD rs563647959
- V129I (p.Val129Ile), cosmic curated COSV10525, ExAC rs563647959, gnomAD rs563647959, REVEL 0.81, CADD 26.30
- D131E (p.Asp131Glu), TOPMed rs1338174387, gnomAD rs1338174387, REVEL 0.42, CADD 22.80
- D131G (p.Asp131Gly), NCI-TCGA TCGA novel, REVEL 0.90, CADD 29.90, Variant assessed as somatic; moderate impact.
- K132E (p.Lys132Glu), TOPMed rs2045911693, REVEL 0.83, CADD 29.20
- K132T (p.Lys132Thr), ExAC rs761373193, gnomAD rs761373193, REVEL 0.85, CADD 28.90
- C133Y (p.Cys133Tyr), Ensembl rs2145964958
- K134E (p.Lys134Glu), gnomAD rs1224230940, REVEL 0.81, CADD 28.00
- K134R (p.Lys134Arg), 1000Genomes rs576712021, ExAC rs576712021, TOPMed rs576712021, gnomAD rs576712021, REVEL 0.62, CADD 25.00, Likely benign, Alzheimer disease
- H137Q (p.His137Gln), TOPMed rs2045911066
- Q138R (p.Gln138Arg), TOPMed rs1451050785, gnomAD rs1451050785, REVEL 0.72, CADD 25.00, Uncertain significance, APP-related disorder
- E139V (p.Glu139Val), ExAC rs746947550, gnomAD rs746947550, REVEL 0.96, CADD 33.00
- R140T (p.Arg140Thr), rs772020679, ClinGen CA9987655, ClinVar RCV003622218, ExAC rs772020679, REVEL 0.74, CADD 26.00, Uncertain significance, Alzheimer disease
- M141K (p.Met141Lys), ExAC rs745588837, gnomAD rs745588837, REVEL 0.92, CADD 27.30
- M141T (p.Met141Thr), ExAC rs745588837, gnomAD rs745588837, REVEL 0.90, CADD 26.20
- M141V (p.Met141Val), Ensembl rs200086074, REVEL 0.76, CADD 27.40
- D142G (p.Asp142Gly), cosmic curated COSV60998, ExAC rs779288025, gnomAD rs779288025, REVEL 0.79, CADD 32.00
- V143I (p.Val143Ile), rs200541360, Ensembl rs200541360, REVEL 0.33, CADD 19.40, Variant assessed as somatic; moderate impact.
- C144W (p.Cys144Trp), ExAC rs199520480, TOPMed rs199520480, gnomAD rs199520480, REVEL 0.90, CADD 23.50, Likely benign
- E145K (p.Glu145Lys), rs201573490, ClinGen CA319558398, NCI-TCGA Cosmic COSV6099, cosmic curated COSV60994, REVEL 0.84, CADD 25.40, Uncertain significance, not specified; Alzheimer disease
- H147Y (p.His147Tyr), cosmic curated COSV10069, Ensembl rs2145964739
- H149R (p.His149Arg), rs200857049, ClinGen CA319558397, ClinVar RCV002662840, TOPMed rs200857049, REVEL 0.90, CADD 24.40, Uncertain significance, Alzheimer disease
- W150* (p.Trp150Ter), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61005, Variant assessed as somatic; high impact.
- H151Y (p.His151Tyr), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61002, TOPMed rs2045909097, Variant assessed as somatic; moderate impact.
- T152A (p.Thr152Ala), ExAC rs756629390, gnomAD rs756629390, REVEL 0.40, CADD 22.50
- T152I (p.Thr152Ile), gnomAD rs1459435816, REVEL 0.80, CADD 26.50
- V153I (p.Val153Ile), rs201454946, ExAC rs201454946, TOPMed rs201454946, gnomAD rs201454946, REVEL 0.47, CADD 22.50, Uncertain significance, Alzheimer disease
- A154T (p.Ala154Thr), cosmic curated COSV10816, NCI-TCGA TCGA novel, TOPMed rs2045908080, Variant assessed as somatic; moderate impact.
- K155R (p.Lys155Arg), rs2045907801, ClinGen CA409863130, ClinVar RCV002263275, Ensembl rs2045907801, AlphaMissense 0.12, MetaLR 0.89, Uncertain significance, not provided
- T157I (p.Thr157Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C158Y (p.Cys158Tyr), rs771319862, NCI-TCGA Cosmic COSV6099, cosmic curated COSV60994, ExAC rs771319862, AlphaMissense 1.00, MetaLR 0.52, Variant assessed as somatic; moderate impact.
- S159G (p.Ser159Gly), gnomAD rs1212082541, REVEL 0.36, CADD 20.40
- S159N (p.Ser159Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E160K (p.Glu160Lys), ESP rs375376201, TOPMed rs375376201, gnomAD rs375376201, REVEL 0.48, CADD 22.10, Conflicting interpretations, Inborn genetic diseases; Alzheimer disease
- K161E (p.Lys161Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K161R (p.Lys161Arg), Ensembl rs200892475, REVEL 0.40, CADD 21.60
- S162N (p.Ser162Asn), Ensembl rs200117824
- T163S (p.Thr163Ser), ExAC rs749504313, gnomAD rs749504313, REVEL 0.50, CADD 23.30
- N164I (p.Asn164Ile), gnomAD rs1231783932, REVEL 0.68, CADD 23.70, Uncertain significance, Inborn genetic diseases
- N164S (p.Asn164Ser), rs1231783932, ClinGen CA409863056, ClinVar RCV000658921, gnomAD rs1231783932, REVEL 0.35, CADD 17.80, Uncertain significance, not provided
- H166Y (p.His166Tyr), rs201885206, ClinGen CA9987630, ClinVar RCV002623266, ExAC rs201885206, REVEL 0.76, CADD 25.20, Uncertain significance, Alzheimer disease
- D167H (p.Asp167His), Ensembl rs2045822704
- G169C (p.Gly169Cys), NCI-TCGA Cosmic COSV6100, Variant assessed as somatic; moderate impact.
- G169D (p.Gly169Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G169S (p.Gly169Ser), rs201102339, NCI-TCGA Cosmic COSV6100, cosmic curated COSV61006, ExAC rs201102339, REVEL 0.95, CADD 27.90, Variant assessed as somatic; moderate impact.
- G169V (p.Gly169Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M170I (p.Met170Ile), rs372642708, ClinGen CA9987627, ClinVar RCV002958001, ClinVar RCV004790285, REVEL 0.91, CADD 26.30, Conflicting interpretations, not provided; Inborn genetic diseases; Alzheimer disease
- L172Q (p.Leu172Gln), gnomAD rs2045821993, REVEL 0.98, CADD 30.00
- P173L (p.Pro173Leu), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61002, Variant assessed as somatic; moderate impact.
- G175R (p.Gly175Arg), TOPMed rs201817335, gnomAD rs201817335, REVEL 0.88, CADD 28.70
- I176F (p.Ile176Phe), TOPMed rs1205098782, gnomAD rs1205098782
- I176V (p.Ile176Val), TOPMed rs1205098782, gnomAD rs1205098782, REVEL 0.52, CADD 21.10
- D177E (p.Asp177Glu), TOPMed rs1431982540, gnomAD rs1431982540, REVEL 0.91, CADD 24.40
- K178M (p.Lys178Met), ExAC rs758637653, TOPMed rs758637653, gnomAD rs758637653, REVEL 0.75, CADD 29.10, Uncertain significance
- K178N (p.Lys178Asn), rs2516934402, ClinGen CA409862957, ClinVar RCV003621930, Uncertain significance, Alzheimer disease
- K178R (p.Lys178Arg), rs758637653, ClinGen CA409862959, NCI-TCGA Cosmic COSV6099, cosmic curated COSV60998, REVEL 0.48, CADD 21.90, Uncertain significance, Alzheimer disease
- R180* (p.Arg180Ter), cosmic curated COSV60999, ExAC rs753562272, gnomAD rs753562272, CADD 37.00
- R180L (p.Arg180Leu), ExAC rs200898059, TOPMed rs200898059, gnomAD rs200898059
- R180Q (p.Arg180Gln), cosmic curated COSV60997, ExAC rs200898059, TOPMed rs200898059, gnomAD rs200898059, REVEL 0.82, CADD 29.20, Uncertain significance, Alzheimer disease
- G181R (p.Gly181Arg), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, Variant assessed as somatic; moderate impact.
- V182A (p.Val182Ala), TOPMed rs771317418, gnomAD rs771317418, REVEL 0.87, CADD 28.00
- V182I (p.Val182Ile), Ensembl rs202108340
- E183Q (p.Glu183Gln), NCI-TCGA Cosmic COSV6099, cosmic curated COSV60997, Variant assessed as somatic; moderate impact.
- F184L (p.Phe184Leu), rs760249418, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, NCI-TCGA Cosmic COSV6099, AlphaMissense 1.00, MetaLR 0.93, Variant assessed as somatic; moderate impact.
- P188L (p.Pro188Leu), rs2516934188, ClinGen CA409862895, ClinVar RCV003622162, Uncertain significance, Alzheimer disease
- P188S (p.Pro188Ser), TOPMed rs199744129, gnomAD rs199744129, REVEL 0.94, CADD 29.10
- L189M (p.Leu189Met), rs1208508997, ClinGen CA409862894, ClinVar RCV002785909, AlphaMissense 0.06, MetaLR 0.02, Uncertain significance, Alzheimer disease
Public APP analysis runs
- APP analysis run — APP (1,078 variants) — completed 2026-08-10