IAPP (Islet amyloid polypeptide) variants and mutations
IAPP (also known as Islet amyloid polypeptide) is a human protein-coding gene encoding an islet amyloid polypeptide protein. It is cosecreted with insulin from pancreatic beta cells and helps regulate satiety, gastric emptying, and postprandial glucose handling. In type 2 diabetes, misfolded amylin can form amyloid deposits within pancreatic islets and contribute to beta-cell stress. This analysis covers 292 IAPP variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes AL amyloidosis, Alzheimer disease, and diabetes mellitus. Example IAPP variants include M1?, G2C, and G2D.
Variant analysis overview
- Gene: IAPP
- Protein: Islet amyloid polypeptide
- UniProt accession: P10997
- Organism: Homo sapiens
- Variants analyzed: 292
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 142 unspecified-consequence records; 89 missense variants; 38 synonymous variants; 16 frameshift variants; 6 stop-gained variants; 2 splice-region variants; 2 substitution
- Prediction scores: 235 variants have prediction scores (80% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: AL amyloidosis, Alzheimer disease, diabetes mellitus, type 2 diabetes mellitus, metabolic syndrome, gout, hypertensive disorder, hydrops fetalis, complication, obesity due to melanocortin 4 receptor deficiency, hemorrhage, infection.
Protein structure and variant hotspots
- Protein features: 1 post-translational modification sites.
- PTM context: 2 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable IAPP variants
Examples include M1?, G2C, G2D, G2S, I3F, I3T, I3I, L4L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10727
- G2C (p.Gly2Cys), ExAC rs557866734, TOPMed rs557866734, gnomAD rs557866734
- G2D (p.Gly2Asp), cosmic curated COSV53713, REVEL 0.26, CADD 7.52
- G2S (p.Gly2Ser), cosmic curated COSV10587, ExAC rs557866734, TOPMed rs557866734, gnomAD rs557866734, REVEL 0.13, CADD 6.55
- I3F (p.Ile3Phe), gnomAD rs1161915805, REVEL 0.18, CADD 7.15
- I3T (p.Ile3Thr), gnomAD 12-21373359-T-C, REVEL 0.30, CADD 4.44
- I3I (p.Ile3Ile), gnomAD 12-21373360-C-A, CADD 0.84
- L4L (p.Leu4Leu), gnomAD 12-21373361-C-T, CADD 0.67
- K5S (p.Lys5Ser), gnomAD 12-21373363-GA-G, CADD 20.70
- K5K (p.Lys5Lys), gnomAD 12-21373366-G-A, CADD 3.27
- L6M (p.Leu6Met), TOPMed rs1368478122, REVEL 0.34, CADD 20.40
- L6Q (p.Leu6Gln), ESP rs374152437, TOPMed rs374152437, REVEL 0.66, CADD 23.50
- L6R (p.Leu6Arg), ESP rs374152437, TOPMed rs374152437
- L6L (p.Leu6Leu), gnomAD 12-21373369-G-A, CADD 0.68
- Q7R (p.Gln7Arg), 1000Genomes rs200933325, ESP rs200933325, ExAC rs200933325, TOPMed rs200933325, REVEL 0.15, CADD 13.80
- Q7* (p.Gln7Ter), gnomAD 12-21376333-C-T, CADD 12.20
- Q7K (p.Gln7Lys), rs1002059648, gnomAD 12-21376333-C-A, CADD 8.74
- Q7H (p.Gln7His), gnomAD 12-21376335-A-T, CADD 6.79
- V8A (p.Val8Ala), TOPMed rs1416344280, gnomAD rs1416344280, REVEL 0.14, CADD 10.20
- V8E (p.Val8Glu), cosmic curated COSV10958
- V8I (p.Val8Ile), gnomAD 12-21373373-G-A, REVEL 0.08, CADD 3.22
- V8L (p.Val8Leu), gnomAD 12-21373373-G-T, REVEL 0.12, CADD 5.59
- F9L (p.Phe9Leu), cosmic curated COSV53713, REVEL 0.22, CADD 0.94
- F9S (p.Phe9Ser), gnomAD 12-21373377-T-C, REVEL 0.37, CADD 13.30
- F9I (p.Phe9Ile), rs551847146, gnomAD 12-21376345-T-A, CADD 4.39
- F9F (p.Phe9Phe), gnomAD 12-21376347-T-C, CADD 6.69
- L10F (p.Leu10Phe), cosmic curated COSV10459
- L10I (p.Leu10Ile), NCI-TCGA Cosmic COSV5371, cosmic curated COSV53714, Variant assessed as somatic; moderate impact.
- L10L (p.Leu10Leu), rs762274695, gnomAD 12-21373381-C-A, CADD 1.91
- L10M (p.Leu10Met), gnomAD 12-21376327-T-A, CADD 4.55
- I11L (p.Ile11Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I11T (p.Ile11Thr), Ensembl rs925033934, REVEL 0.18, CADD 14.20
- I11V (p.Ile11Val), Ensembl rs773946611, REVEL 0.12, CADD 1.80
- I11I (p.Ile11Ile), rs767861030, gnomAD 12-21373384-T-C, CADD 0.25
- V12C (p.Val12Cys), rs1939941547, gnomAD 12-21373384-TG-T, CADD 15.00
- V12L (p.Val12Leu), gnomAD 12-21373385-G-C, REVEL 0.09, CADD 1.97
- V12V (p.Val12Val), gnomAD 12-21373387-G-A, CADD 0.59
- L13F (p.Leu13Phe), rs373616376, ClinGen CA6477945, ClinVar RCV004168069, ESP rs373616376, REVEL 0.19, CADD 7.40, Uncertain significance, not specified
- L13P (p.Leu13Pro), ExAC rs754564502, TOPMed rs754564502, gnomAD rs754564502, REVEL 0.56, CADD 15.40
- L13L (p.Leu13Leu), gnomAD 12-21373390-C-T, CADD 1.76
- S14C (p.Ser14Cys), gnomAD rs1367248248, REVEL 0.16, CADD 7.34
- S14Y (p.Ser14Tyr), cosmic curated COSV99557, REVEL 0.31, CADD 13.10
- V15A (p.Val15Ala), ExAC rs778403247, TOPMed rs778403247, gnomAD rs778403247, REVEL 0.15, CADD 13.40
- V15I (p.Val15Ile), NCI-TCGA Cosmic COSV9955, cosmic curated COSV99557, Variant assessed as somatic; moderate impact.
- V15L (p.Val15Leu), gnomAD 12-21373394-G-C, REVEL 0.12, CADD 1.47
- V15F (p.Val15Phe), gnomAD 12-21376351-G-T, CADD 5.19
- V15V (p.Val15Val), gnomAD 12-21376353-T-C, CADD 9.25
- A16V (p.Ala16Val), Ensembl rs1591894861, REVEL 0.14, CADD 14.10
- A16A (p.Ala16Ala), rs1273239812, gnomAD 12-21373399-A-G, CADD 2.96
- L17* (p.Leu17Ter), TOPMed rs904381884, gnomAD rs904381884, CADD 35.00
- L17F (p.Leu17Phe), NCI-TCGA Cosmic COSV5371, cosmic curated COSV53713, Variant assessed as somatic; moderate impact.
- L17L (p.Leu17Leu), rs548820504, gnomAD 12-21373400-T-C, CADD 0.87
- N18D (p.Asn18Asp), gnomAD rs1262493141, REVEL 0.06, CADD 9.69
- N18K (p.Asn18Lys), TOPMed rs987849270, gnomAD rs987849270, REVEL 0.04, CADD 7.85
- N18T (p.Asn18Thr), gnomAD 12-21373401-TG-T, CADD 13.90
- N18Y (p.Asn18Tyr), gnomAD 12-21373403-A-T, REVEL 0.10, CADD 15.40
- N18I (p.Asn18Ile), gnomAD 12-21376360-GA-G, CADD 5.07
- N18S (p.Asn18Ser), gnomAD 12-21376364-A-G, CADD 4.98
- H19P (p.His19Pro), TOPMed rs1279799238, gnomAD rs1279799238, REVEL 0.28, CADD 8.11
- H19R (p.His19Arg), cosmic curated COSV53712, TOPMed rs1279799238, gnomAD rs1279799238, REVEL 0.12, CADD 5.57
- H19Y (p.His19Tyr), TOPMed rs1939944426, REVEL 0.17, CADD 2.05
- H19N (p.His19Asn), gnomAD 12-21373406-C-A, REVEL 0.07, CADD 3.52
- H19H (p.His19His), gnomAD 12-21373408-T-C, CADD 0.61
- L20M (p.Leu20Met), cosmic curated COSV99557
- L20P (p.Leu20Pro), ExAC rs758292552, gnomAD rs758292552, REVEL 0.63, CADD 24.20
- L20V (p.Leu20Val), TOPMed rs1939944998, REVEL 0.41, CADD 18.40
- K21* (p.Lys21Ter), cosmic curated COSV53713
- A22A (p.Ala22Ala), rs62871062, gnomAD 12-21373417-T-C, CADD 6.07
- T23I (p.Thr23Ile), Ensembl rs1939945928, REVEL 0.10, CADD 19.10, Uncertain significance, not specified
- T23P (p.Thr23Pro), TOPMed rs1939945451
- T23K (p.Thr23Lys), gnomAD 12-21373419-C-A, REVEL 0.11, CADD 15.80
- T23A (p.Thr23Ala), gnomAD 12-21376348-A-G, CADD 1.57
- T23S (p.Thr23Ser), gnomAD 12-21376348-A-T, CADD 2.90
- T23N (p.Thr23Asn), gnomAD 12-21376349-C-A, CADD 3.71
- T23T (p.Thr23Thr), rs1940190287, gnomAD 12-21376350-T-C, CADD 7.95
- P24T (p.Pro24Thr), cosmic curated COSV10727, Ensembl rs1939946146
- P24H (p.Pro24His), rs1565521110, gnomAD 12-21373417-T-TAC, CADD 23.00
- P24L (p.Pro24Leu), gnomAD 12-21373422-C-T, REVEL 0.16, CADD 16.30
- P24P (p.Pro24Pro), gnomAD 12-21373660-A-G, CADD 7.24
- P24Q (p.Pro24Gln), gnomAD 12-21373704-C-A, CADD 8.40
- I25N (p.Ile25Asn), cosmic curated COSV53713
- I25S (p.Ile25Ser), TOPMed rs1939946378
- I25T (p.Ile25Thr), TOPMed rs1939946378, REVEL 0.16, CADD 8.23
- I25H (p.Ile25His), gnomAD 12-21373420-A-AC, CADD 22.40
- I25M (p.Ile25Met), gnomAD 12-21373426-T-G, REVEL 0.20, CADD 0.84
- I25F (p.Ile25Phe), gnomAD 12-21373653-TA-T, CADD 5.44
- I25V (p.Ile25Val), rs1259753597, gnomAD 12-21373655-A-G, CADD 6.93
- I25R (p.Ile25Arg), gnomAD 12-21373677-T-G, CADD 2.39
- E26Q (p.Glu26Gln), gnomAD 12-21373427-G-C, REVEL 0.18, CADD 13.30
- E26K (p.Glu26Lys), gnomAD 12-21376360-G-A, CADD 13.60
- E26* (p.Glu26Ter), gnomAD 12-21376360-G-T, CADD 15.20
- E26G (p.Glu26Gly), rs1940190878, gnomAD 12-21376361-A-G, CADD 7.44
- E26E (p.Glu26Glu), gnomAD 12-21376362-A-G, CADD 3.94
- S27N (p.Ser27Asn), rs1286099292, NCI-TCGA Cosmic COSV5371, cosmic curated COSV53714, Ensembl rs1286099292, AlphaMissense 0.13, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- S27R (p.Ser27Arg), ExAC rs780362061, TOPMed rs780362061, gnomAD rs780362061, REVEL 0.12, CADD 22.40
- S27T (p.Ser27Thr), gnomAD 12-21373667-T-A, CADD 2.87
- S27P (p.Ser27Pro), gnomAD 12-21373667-T-C, CADD 3.42
- S27* (p.Ser27Ter), gnomAD 12-21373668-C-A, CADD 11.70
- S27S (p.Ser27Ser), rs182577227, gnomAD 12-21373669-A-G, CADD 15.00
- H28N (p.His28Asn), NCI-TCGA TCGA novel, REVEL 0.09, CADD 23.90, Variant assessed as somatic; moderate impact.
- H28R (p.His28Arg), ExAC rs749463838, gnomAD rs749463838, REVEL 0.10, CADD 17.50
- H28Q (p.His28Gln), gnomAD 12-21378240-T-A, REVEL 0.09, CADD 21.50
- Q29E (p.Gln29Glu), NCI-TCGA Cosmic COSV5371, cosmic curated COSV53713, Variant assessed as somatic; moderate impact.
- Q29H (p.Gln29His), NCI-TCGA TCGA novel, TOPMed rs1940349477, Variant assessed as somatic; moderate impact.
- Q29R (p.Gln29Arg), TOPMed rs1940349282
- Q29Q (p.Gln29Gln), gnomAD 12-21373645-G-A, CADD 9.50
- Q29K (p.Gln29Lys), gnomAD 12-21376351-GT-G, CADD 4.20
- V30I (p.Val30Ile), rs1685721841, gnomAD 12-21373661-G-A, CADD 6.65
- V30D (p.Val30Asp), gnomAD 12-21373662-T-A, CADD 9.78
- E31E (p.Glu31Glu), gnomAD 12-21373687-A-G, CADD 11.30
- E31* (p.Glu31Ter), gnomAD 12-21373706-G-T, CADD 7.44
- E31D (p.Glu31Asp), gnomAD 12-21373708-A-T, CADD 3.44
- E31K (p.Glu31Lys), rs1414845423, gnomAD 12-21373712-G-A, CADD 6.93
- E31A (p.Glu31Ala), gnomAD 12-21378248-A-C, REVEL 0.12, CADD 25.30
- K32R (p.Lys32Arg), Ensembl rs1940349963
- K32E (p.Lys32Glu), gnomAD 12-21378250-A-G, REVEL 0.27, CADD 25.70
- R33P (p.Arg33Pro), ExAC rs200996235, TOPMed rs200996235, gnomAD rs200996235, REVEL 0.34, CADD 26.00
- R33Q (p.Arg33Gln), rs200996235, NCI-TCGA Cosmic COSV5371, cosmic curated COSV53714, ExAC rs200996235, REVEL 0.28, CADD 26.70, Uncertain significance, not specified
- R33W (p.Arg33Trp), TOPMed rs1370833713, gnomAD rs1370833713, REVEL 0.18, CADD 23.10
- R33E (p.Arg33Glu), rs748128579, gnomAD 12-21373668-CA-C, CADD 12.70
- R33G (p.Arg33Gly), rs1409685287, gnomAD 12-21373670-A-G, CADD 14.60
- R33I (p.Arg33Ile), rs1377330495, gnomAD 12-21373671-G-T, CADD 17.30
- R33K (p.Arg33Lys), rs1377330495, gnomAD 12-21373671-G-A, CADD 16.80
- R33S (p.Arg33Ser), rs976582409, gnomAD 12-21373672-A-T, CADD 18.80
- R33R (p.Arg33Arg), gnomAD 12-21376323-A-G, CADD 1.61
- K34R (p.Lys34Arg), rs1388060400, gnomAD 12-21373701-A-G, CADD 11.40
- K34T (p.Lys34Thr), gnomAD 12-21373701-A-C, CADD 12.60
- K34N (p.Lys34Asn), gnomAD 12-21373702-G-T, CADD 5.00
- K34E (p.Lys34Glu), gnomAD 12-21378256-A-G, REVEL 0.20, CADD 25.60
- C35R (p.Cys35Arg), cosmic curated COSV10727
- C35F (p.Cys35Phe), gnomAD 12-21376325-G-T, CADD 1.10
- C35Y (p.Cys35Tyr), gnomAD 12-21376325-G-A, CADD 3.10
- C35C (p.Cys35Cys), gnomAD 12-21376326-T-C, CADD 8.66
- N36S (p.Asn36Ser), Ensembl rs2137113837, REVEL 0.10, CADD 21.50
- N36Y (p.Asn36Tyr), ESP rs142526620, ExAC rs142526620, TOPMed rs142526620, gnomAD rs142526620, REVEL 0.19, CADD 20.60
- N36H (p.Asn36His), gnomAD 12-21378262-A-C, REVEL 0.21, CADD 23.10
- T37P (p.Thr37Pro), Ensembl rs78822118
- A38T (p.Ala38Thr), gnomAD 12-21378268-G-A, REVEL 0.37, CADD 23.70
- T39I (p.Thr39Ile), cosmic curated COSV53714
- T39S (p.Thr39Ser), cosmic curated COSV53713
- C40R (p.Cys40Arg), cosmic curated COSV53714, Ensembl rs1940351821, REVEL 0.58, CADD 23.60
- C40S (p.Cys40Ser), Ensembl rs1940351821
- A41E (p.Ala41Glu), ExAC rs773593660, TOPMed rs773593660, gnomAD rs773593660
- A41V (p.Ala41Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T42A (p.Thr42Ala), NCI-TCGA Cosmic COSV5371, cosmic curated COSV53713, REVEL 0.38, CADD 23.20, Variant assessed as somatic; moderate impact.
- T42K (p.Thr42Lys), ExAC rs761079012, TOPMed rs761079012, gnomAD rs761079012, REVEL 0.26, CADD 18.20
- T42M (p.Thr42Met), rs761079012, NCI-TCGA Cosmic COSV5371, cosmic curated COSV53714, ExAC rs761079012, REVEL 0.20, CADD 9.11, Variant assessed as somatic; moderate impact.
- Q43* (p.Gln43Ter), Ensembl rs1940353165, CADD 36.00
- Q43R (p.Gln43Arg), ExAC rs775281880, TOPMed rs775281880, gnomAD rs775281880, REVEL 0.34, CADD 23.90
- Q43L (p.Gln43Leu), rs1940352390, gnomAD 12-21378279-A-T, CADD 0.39
- Q43K (p.Gln43Lys), gnomAD 12-21378283-C-A, REVEL 0.26, CADD 23.00
- R44C (p.Arg44Cys), rs763676184, NCI-TCGA Cosmic COSV5371, cosmic curated COSV53713, ExAC rs763676184, REVEL 0.23, CADD 23.10, Variant assessed as somatic; moderate impact.
- R44G (p.Arg44Gly), ExAC rs763676184, TOPMed rs763676184, gnomAD rs763676184, REVEL 0.28, CADD 24.20
- R44H (p.Arg44His), cosmic curated COSV53713, ExAC rs773900669, TOPMed rs773900669, gnomAD rs773900669, REVEL 0.13, CADD 23.20
- R44S (p.Arg44Ser), ExAC rs763676184, TOPMed rs763676184, gnomAD rs763676184, REVEL 0.26, CADD 22.10
- R44T (p.Arg44Thr), rs932545696, gnomAD 12-21373692-G-C, CADD 1.51
- R44L (p.Arg44Leu), gnomAD 12-21378287-G-T, REVEL 0.26, CADD 24.80
- R44P (p.Arg44Pro), gnomAD 12-21378287-G-C, REVEL 0.35, CADD 26.50
- L45P (p.Leu45Pro), gnomAD rs1484149172, REVEL 0.69, CADD 27.10
- L45L (p.Leu45Leu), gnomAD 12-21373664-T-C, CADD 10.30
- L45F (p.Leu45Phe), gnomAD 12-21373666-G-T, CADD 1.00
- A46E (p.Ala46Glu), gnomAD rs1242505102, CADD 6.79
- A46T (p.Ala46Thr), TOPMed rs1200804343, gnomAD rs1200804343
- A46V (p.Ala46Val), gnomAD rs1242505102, CADD 8.54
- A46S (p.Ala46Ser), gnomAD 12-21373697-G-T, CADD 5.20
- A46G (p.Ala46Gly), gnomAD 12-21378293-C-G, REVEL 0.15, CADD 23.50
- N47D (p.Asn47Asp), NCI-TCGA Cosmic COSV9955, cosmic curated COSV99557, REVEL 0.07, CADD 15.00, Variant assessed as somatic; moderate impact.
- N47I (p.Asn47Ile), cosmic curated COSV53713
- F48S (p.Phe48Ser), ExAC rs750354470, gnomAD rs750354470
- F48V (p.Phe48Val), cosmic curated COSV10587
- F48Y (p.Phe48Tyr), ExAC rs750354470, gnomAD rs750354470, REVEL 0.27, CADD 23.70
- L49* (p.Leu49Ter), cosmic curated COSV53714
- V50A (p.Val50Ala), gnomAD 12-21378305-T-C, REVEL 0.07, CADD 8.00
- V50V (p.Val50Val), gnomAD 12-21378306-T-A, CADD 8.55
- H51D (p.His51Asp), ESP rs369714240, ExAC rs369714240, TOPMed rs369714240, gnomAD rs369714240, REVEL 0.17, AlphaMissense 0.10
- H51N (p.His51Asn), rs369714240, NCI-TCGA Cosmic COSV9955, cosmic curated COSV99557, AlphaMissense 0.10, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- H51R (p.His51Arg), TOPMed rs1940357141
- H51Y (p.His51Tyr), rs369714240, NCI-TCGA Cosmic COSV9955, cosmic curated COSV99557, REVEL 0.03, AlphaMissense 0.10, Variant assessed as somatic; moderate impact.
- H51Q (p.His51Gln), gnomAD 12-21373710-ATG-A, CADD 4.06
- S52F (p.Ser52Phe), cosmic curated COSV10501
Public IAPP analysis runs
- IAPP analysis run — IAPP (292 variants) — completed 2026-08-21