PPARG (P37231) variants and mutations
PPARG (also known as P37231) is a human protein-coding gene encoding a peroxisome proliferator-activated receptor gamma protein. It drives adipocyte differentiation, lipid storage, and insulin-sensitive metabolic programs in response to endogenous lipids and thiazolidinedione drugs. Dominant-negative variants cause familial partial lipodystrophy type 3 with severe insulin resistance and dyslipidemia. This analysis covers 403 PPARG variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes type 2 diabetes mellitus, PPARG-related familial partial lipodystrophy, and diabetes mellitus. Example PPARG variants include M1?, M1V, and M1T.
Variant analysis overview
- Gene: PPARG
- Protein: P37231
- UniProt accession: P37231
- Organism: Homo sapiens
- Variants analyzed: 403
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 121 unspecified-consequence records; 196 missense variants; 70 synonymous variants; 6 frameshift variants; 5 stop-gained variants; 3 splice-region variants; 1 in-frame deletions; 1 substitution
- Prediction scores: 317 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: type 2 diabetes mellitus, PPARG-related familial partial lipodystrophy, diabetes mellitus, ulcerative colitis, morbid obesity, Abnormality of the skeletal system, coronary artery disorder, colon carcinoma, obesity disorder, metabolic syndrome, inherited obesity, inherited lipid metabolism disorder.
Protein structure and variant hotspots
- Protein features: 1 domains; 4 binding sites; 2 post-translational modification sites.
- Structural context: 64 variants have structural context.
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 PPARG variants
Examples include M1?, M1V, M1T, G2S, G2V, E3K, E3Q, E3G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5514, Variant assessed as somatic; high impact.
- M1V (p.Met1Val), rs1464788240, gnomAD 3-12379727-A-G, CADD 21.50, PolyPhen-2 0.09
- M1T (p.Met1Thr), rs748119466, gnomAD 3-12379728-T-C, CADD 22.10, PolyPhen-2 0.01
- G2S (p.Gly2Ser), gnomAD 3-12351596-G-A, CADD 23.20
- G2V (p.Gly2Val), gnomAD 3-12351597-G-T, CADD 23.10
- E3K (p.Glu3Lys), NCI-TCGA Cosmic COSV5514, gnomAD rs2048487795, CADD 23.30, Variant assessed as somatic; moderate impact.
- E3Q (p.Glu3Gln), rs1246297562, gnomAD 3-12379724-G-C, CADD 19.40, PolyPhen-2 0.06
- E3G (p.Glu3Gly), rs1186361559, gnomAD 3-12379725-A-G, CADD 28.50
- T4S (p.Thr4Ser), gnomAD 3-12351602-A-T, CADD 22.10
- T4T (p.Thr4Thr), gnomAD 3-12379723-A-G, CADD 3.63
- L5V (p.Leu5Val), rs928058229, gnomAD 3-12351605-C-G, CADD 15.00
- L5L (p.Leu5Leu), rs760515031, gnomAD 3-12351607-G-A, CADD 9.10
- G6E (p.Gly6Glu), gnomAD 3-12351609-G-A, CADD 22.50
- G6G (p.Gly6Gly), rs1295753353, gnomAD 3-12379753-G-A, CADD 6.68
- D7E (p.Asp7Glu), NCI-TCGA Cosmic COSV9982, Variant assessed as somatic; moderate impact.
- D7V (p.Asp7Val), gnomAD 3-12351612-A-T, CADD 22.10
- D7G (p.Asp7Gly), rs1447983492, gnomAD 3-12351612-A-G, CADD 22.50
- D7D (p.Asp7Asp), gnomAD 3-12351613-T-C, CADD 5.96
- D7N (p.Asp7Asn), rs1215582219, gnomAD 3-12379718-G-A, AlphaMissense 0.71, MetaLR 0.39
- S8F (p.Ser8Phe), NCI-TCGA TCGA novel, CADD 22.30, Variant assessed as somatic; moderate impact.
- S8A (p.Ser8Ala), gnomAD 3-12351614-T-G, CADD 0.49
- S8S (p.Ser8Ser), gnomAD 3-12351616-T-C, CADD 11.40
- P9T (p.Pro9Thr), gnomAD 3-12351617-C-A, CADD 16.00
- P9S (p.Pro9Ser), rs2048488773, gnomAD 3-12351617-C-T, CADD 16.50
- P9P (p.Pro9Pro), rs755878073, gnomAD 3-12379732-A-C, CADD 3.58
- I10V (p.Ile10Val), rs776891749, gnomAD 3-12351620-A-G, CADD 1.73
- I10T (p.Ile10Thr), rs1487931740, gnomAD 3-12351621-T-C, CADD 15.00
- I10I (p.Ile10Ile), rs761891193, gnomAD 3-12351622-T-C, CADD 9.90
- I10F (p.Ile10Phe), rs143370807, gnomAD 3-12379754-A-T, CADD 23.00, PolyPhen-2 0.08
- D11Y (p.Asp11Tyr), rs765473307, gnomAD 3-12351623-G-T, CADD 25.20
- D11D (p.Asp11Asp), rs1329838398, gnomAD 3-12351625-C-T, CADD 9.39
- P12A (p.Pro12Ala), rs1801282, ClinGen CA154763, ClinVar RCV000118044, ClinVar RCV000300998, CADD 15.10, Benign/Likely benign, not specified; not provided; PPARG-related familial partial lipodystrophy
- P12T (p.Pro12Thr), gnomAD 3-12351626-C-A, CADD 19.00
- E13* (p.Glu13Ter), NCI-TCGA Cosmic COSV5514, Variant assessed as somatic; high impact.
- S14G (p.Ser14Gly), rs763032994, gnomAD 3-12351632-A-G, CADD 13.70
- S14N (p.Ser14Asn), rs1055170892, gnomAD 3-12351633-G-A, CADD 16.40
- S14S (p.Ser14Ser), rs145161478, gnomAD 3-12351634-C-T, CADD 1.51
- D15Y (p.Asp15Tyr), rs943725719, gnomAD 3-12351635-G-T, CADD 15.10
- D15N (p.Asp15Asn), rs943725719, gnomAD 3-12351635-G-A, CADD 14.60
- D15D (p.Asp15Asp), gnomAD 3-12351637-T-C, CADD 6.67
- S16Y (p.Ser16Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S16T (p.Ser16Thr), gnomAD 3-12351635-GATTCC, CADD 24.10
- S16C (p.Ser16Cys), rs2048489977, gnomAD 3-12351635-GATTCC, CADD 24.10
- S16F (p.Ser16Phe), rs560683642, gnomAD 3-12351639-C-T, CADD 18.30
- S16S (p.Ser16Ser), rs1040659276, gnomAD 3-12351640-C-T, CADD 10.50
- S16G (p.Ser16Gly), gnomAD 3-12379757-A-G, CADD 18.60, PolyPhen-2 0.01
- S16A (p.Ser16Ala), gnomAD 3-12379760-T-G, CADD 18.30, PolyPhen-2 0.00
- F17V (p.Phe17Val), gnomAD 3-12351641-T-G, CADD 22.50
- F17L (p.Phe17Leu), rs752068471, gnomAD 3-12351643-C-A, CADD 13.70
- F17F (p.Phe17Phe), rs752068471, gnomAD 3-12351643-C-T, CADD 9.19
- F17I (p.Phe17Ile), gnomAD 3-12379748-T-A, CADD 24.30, PolyPhen-2 0.17
- T18T (p.Thr18Thr), rs1294325666, gnomAD 3-12351646-T-G, CADD 7.14
- D19Y (p.Asp19Tyr), gnomAD 3-12351647-G-T, CADD 21.50
- D19V (p.Asp19Val), gnomAD 3-12351648-A-T, CADD 16.00
- D19D (p.Asp19Asp), rs755335866, gnomAD 3-12351649-T-C, CADD 5.76
- D19N (p.Asp19Asn), rs777067241, gnomAD 3-12379766-G-A, CADD 27.10, PolyPhen-2 0.92
- D19A (p.Asp19Ala), rs762280243, gnomAD 3-12379767-A-C, CADD 27.10, PolyPhen-2 0.89
- D19E (p.Asp19Glu), rs138038967, gnomAD 3-12379768-T-G, CADD 12.40, PolyPhen-2 0.17
- D19H (p.Asp19His), gnomAD 3-12379784-G-C, CADD 26.80, PolyPhen-2 0.89
- D19G (p.Asp19Gly), rs756002554, gnomAD 3-12379785-A-G, CADD 25.90
- T20N (p.Thr20Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T20R (p.Thr20Arg), gnomAD 3-12351649-T-TAG, CADD 20.00
- T20A (p.Thr20Ala), gnomAD 3-12351650-A-G, CADD 6.20
- T20K (p.Thr20Lys), gnomAD 3-12351651-C-A, CADD 16.00
- T20T (p.Thr20Thr), gnomAD 3-12351652-A-G, CADD 5.95
- L21Q (p.Leu21Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L21L (p.Leu21Leu), rs572991054, gnomAD 3-12351653-C-T, CADD 8.04
- L21P (p.Leu21Pro), gnomAD 3-12351654-T-C, CADD 22.60
- L21V (p.Leu21Val), rs751292113, gnomAD 3-12379769-C-G, CADD 22.30, PolyPhen-2 0.07
- L21R (p.Leu21Arg), rs1235373823, gnomAD 3-12379770-T-G, CADD 26.00, PolyPhen-2 0.91
- S22Y (p.Ser22Tyr), gnomAD 3-12351657-C-A, CADD 22.40
- S22F (p.Ser22Phe), rs372494308, gnomAD 3-12379773-C-T, CADD 24.20, PolyPhen-2 0.85
- S22S (p.Ser22Ser), rs150513215, gnomAD 3-12379774-C-T, CADD 0.60
- N24K (p.Asn24Lys), gnomAD 3-12351664-C-A, CADD 12.20
- N24S (p.Asn24Ser), rs375411329, gnomAD 3-12379746-A-G, CADD 18.10, PolyPhen-2 0.03
- N24T (p.Asn24Thr), rs375411329, gnomAD 3-12379746-A-C, CADD 22.10
- I25V (p.Ile25Val), rs1320029787, gnomAD 3-12351665-A-G, CADD 7.07
- I25T (p.Ile25Thr), gnomAD 3-12351666-T-C, CADD 8.28
- I25N (p.Ile25Asn), rs369178039, gnomAD 3-12379806-T-A, CADD 24.60, PolyPhen-2 0.85
- S26T (p.Ser26Thr), rs753139831, gnomAD 3-12351668-T-A, CADD 4.13
- S26* (p.Ser26Ter), gnomAD 3-12351669-C-A, CADD 36.00
- S26S (p.Ser26Ser), rs1216862524, gnomAD 3-12351670-A-G, CADD 11.30
- S26Y (p.Ser26Tyr), rs868377089, gnomAD 3-12379791-C-A, CADD 24.10, PolyPhen-2 0.58
- Q27E (p.Gln27Glu), gnomAD 3-12351671-C-G, CADD 17.10
- Q27K (p.Gln27Lys), gnomAD 3-12351671-C-A, CADD 18.00
- Q27R (p.Gln27Arg), rs2048491454, gnomAD 3-12351672-A-G, CADD 23.80
- Q27Q (p.Gln27Gln), gnomAD 3-12351673-A-G, CADD 21.90
- E28Q (p.Glu28Gln), gnomAD 3-12351674-G-C, CADD 32.00
- E28G (p.Glu28Gly), gnomAD 3-12379704-A-G, CADD 15.00
- E28V (p.Glu28Val), gnomAD 3-12379782-A-T, CADD 24.50, PolyPhen-2 0.06
- M29V (p.Met29Val), gnomAD 3-12379778-A-G, CADD 15.30, PolyPhen-2 0.04
- M29I (p.Met29Ile), gnomAD 3-12379780-G-A, CADD 22.40, PolyPhen-2 0.04
- T30I (p.Thr30Ile), NCI-TCGA Cosmic COSV9982, cosmic curated COSV99826, Variant assessed as somatic; moderate impact.
- T30A (p.Thr30Ala), gnomAD 3-12379709-A-G, CADD 16.10
- T30N (p.Thr30Asn), rs780983036, gnomAD 3-12379710-C-A, CADD 12.70
- T30T (p.Thr30Thr), gnomAD 3-12379711-C-T, CADD 10.50
- M31I (p.Met31Ile), rs1335787704, gnomAD rs1335787704, AlphaMissense 0.89, MetaLR 0.30, Variant assessed as somatic; moderate impact.
- V32L (p.Val32Leu), rs141797536, gnomAD 3-12379763-G-T, AlphaMissense 0.10, MetaLR 0.06
- V32M (p.Val32Met), rs141797536, gnomAD 3-12379763-G-A, AlphaMissense 0.10, MetaLR 0.06
- V32I (p.Val32Ile), rs149324518, gnomAD 3-12379775-G-A, AlphaMissense 0.07, MetaLR 0.06
- V32V (p.Val32Val), gnomAD 3-12379777-A-G, CADD 2.74
- D33N (p.Asp33Asn), rs1215582219, TOPMed rs1215582219, gnomAD rs1215582219, AlphaMissense 0.71, MetaLR 0.39, Uncertain significance, PPARG-related disorder
- D33D (p.Asp33Asp), rs2049566525, gnomAD 3-12379804-T-C, CADD 10.20
- D33V (p.Asp33Val), gnomAD 3-12379827-A-T, CADD 27.80, PolyPhen-2 1.00
- D33A (p.Asp33Ala), gnomAD 3-12379827-A-C, CADD 27.70, PolyPhen-2 1.00
- T34A (p.Thr34Ala), rs757147631, gnomAD 3-12379817-A-G, CADD 21.90, PolyPhen-2 0.06
- T34T (p.Thr34Thr), rs1453810483, gnomAD 3-12379819-T-C, CADD 11.50
- T34S (p.Thr34Ser), rs2049569356, gnomAD 3-12379821-C-G, CADD 23.40, PolyPhen-2 1.00
- P37S (p.Pro37Ser), NCI-TCGA Cosmic COSV1043, NCI-TCGA Cosmic COSV5514, cosmic curated COSV55140, Variant assessed as somatic; moderate impact.
- P37A (p.Pro37Ala), gnomAD 3-12379811-C-G, CADD 22.90, PolyPhen-2 0.47
- P37R (p.Pro37Arg), gnomAD 3-12379812-C-G, CADD 23.60, PolyPhen-2 0.86
- P37P (p.Pro37Pro), rs1179548759, gnomAD 3-12379813-C-T, CADD 9.38
- F38V (p.Phe38Val), rs1413870551, gnomAD 3-12379829-T-G, CADD 23.90, PolyPhen-2 0.45
- F38F (p.Phe38Phe), gnomAD 3-12379831-C-T, CADD 12.50
- W39R (p.Trp39Arg), rs777492588, gnomAD 3-12379736-T-A, CADD 28.00, PolyPhen-2 0.62
- W39C (p.Trp39Cys), gnomAD 3-12379738-G-C, CADD 26.30, PolyPhen-2 0.87
- P40A (p.Pro40Ala), rs1805192, ClinGen CA119314, ClinVar RCV000008604, UniProt VAR 016116, AlphaMissense 0.10, MetaLR 0.16, Benign
- P40L (p.Pro40Leu), rs2049572135, gnomAD 3-12379848-C-T, CADD 19.10
- P40P (p.Pro40Pro), rs747092130, gnomAD 3-12379849-A-G, CADD 8.05
- T41N (p.Thr41Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T41A (p.Thr41Ala), rs201978569, gnomAD 3-12379844-A-G, CADD 0.02, PolyPhen-2 0.00
- T41P (p.Thr41Pro), rs201978569, gnomAD 3-12379844-A-C, CADD 0.36, PolyPhen-2 0.06
- T41S (p.Thr41Ser), rs201978569, gnomAD 3-12379844-A-T, CADD 0.01, PolyPhen-2 0.00
- T41I (p.Thr41Ile), gnomAD 3-12379845-C-T, CADD 12.40, PolyPhen-2 0.03
- G44A (p.Gly44Ala), NCI-TCGA Cosmic COSV9982, cosmic curated COSV99826, Variant assessed as somatic; moderate impact.
- I45V (p.Ile45Val), gnomAD 3-12379838-A-G, CADD 15.30, PolyPhen-2 0.08
- I45F (p.Ile45Phe), gnomAD 3-12379862-A-T, CADD 14.70, PolyPhen-2 0.12
- I45S (p.Ile45Ser), gnomAD 3-12379863-T-G, CADD 19.40, PolyPhen-2 0.00
- S46P (p.Ser46Pro), gnomAD 3-12379832-T-C, CADD 22.60, PolyPhen-2 0.01
- S46F (p.Ser46Phe), gnomAD 3-12379833-C-T, CADD 25.20, PolyPhen-2 0.60
- S46G (p.Ser46Gly), rs1391398513, gnomAD 3-12379835-A-G, CADD 23.60, PolyPhen-2 0.55
- S46S (p.Ser46Ser), rs573670123, gnomAD 3-12379837-C-T, CADD 10.90
- S46A (p.Ser46Ala), gnomAD 3-12379841-T-G, CADD 23.80, PolyPhen-2 0.97
- S46C (p.Ser46Cys), gnomAD 3-12379842-C-G, CADD 25.20, PolyPhen-2 1.00
- V48M (p.Val48Met), rs141797536, ESP rs141797536, ExAC rs141797536, TOPMed rs141797536, AlphaMissense 0.10, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- D49D (p.Asp49Asp), rs112174008, gnomAD 3-12379861-C-T, CADD 9.54
- L50M (p.Leu50Met), gnomAD 3-12379910-C-A, CADD 20.60, PolyPhen-2 0.02
- L50V (p.Leu50Val), rs1427549233, gnomAD 3-12379910-C-G, CADD 17.60, PolyPhen-2 0.00
- L50P (p.Leu50Pro), gnomAD 3-12379911-T-C, CADD 22.90, PolyPhen-2 0.00
- V52I (p.Val52Ile), rs149324518, ClinGen CA2258094, cosmic curated COSV10804, ClinVar RCV004531724, AlphaMissense 0.07, MetaLR 0.06, Likely benign, not provided
- V52L (p.Val52Leu), rs2049575083, gnomAD 3-12379886-G-T, CADD 1.78
- V52V (p.Val52Val), gnomAD 3-12379888-G-C, CADD 8.35
- E54K (p.Glu54Lys), rs777334819, gnomAD 3-12379856-G-A, AlphaMissense 0.14, MetaLR 0.23
- E54D (p.Glu54Asp), gnomAD 3-12379858-A-C, CADD 17.10, PolyPhen-2 0.00
- D55E (p.Asp55Glu), gnomAD 3-12379882-T-A, CADD 10.50
- H56D (p.His56Asp), rs1441242852, gnomAD 3-12379787-C-G, CADD 19.00, PolyPhen-2 0.01
- H56R (p.His56Arg), rs1559515493, gnomAD 3-12379788-A-G, CADD 17.30, PolyPhen-2 0.29
- H56Q (p.His56Gln), rs1187225480, gnomAD 3-12379789-C-G, CADD 20.30, PolyPhen-2 0.45
- H56N (p.His56Asn), gnomAD 3-12379793-C-A, CADD 20.40, PolyPhen-2 0.02
- H56H (p.His56His), gnomAD 3-12379795-C-T, CADD 7.96
- S59A (p.Ser59Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F60C (p.Phe60Cys), NCI-TCGA Cosmic COSV5514, cosmic curated COSV55143, Variant assessed as somatic; moderate impact.
- F60F (p.Phe60Phe), gnomAD 3-12379870-C-T, CADD 5.69
- D61N (p.Asp61Asn), rs369959243, gnomAD 3-12379895-G-A, CADD 22.90, PolyPhen-2 0.42
- D61G (p.Asp61Gly), rs760238759, gnomAD 3-12379896-A-G, CADD 22.80, PolyPhen-2 0.01
- K63Q (p.Lys63Gln), rs751351168, gnomAD 3-12379805-A-AT, CADD 27.30
- K63K (p.Lys63Lys), rs753619817, gnomAD 3-12379810-G-A, CADD 9.91
- K63E (p.Lys63Glu), rs764018224, gnomAD 3-12379901-A-G, CADD 21.20, PolyPhen-2 0.04
- T66A (p.Thr66Ala), rs375156001, gnomAD 3-12379871-A-G, CADD 3.54
- T66P (p.Thr66Pro), rs375156001, gnomAD 3-12379871-A-C, CADD 6.18, PolyPhen-2 0.00
- T66T (p.Thr66Thr), gnomAD 3-12379879-A-G, CADD 0.62
- V68L (p.Val68Leu), rs765091444, gnomAD 3-12381333-G-T, CADD 12.70, PolyPhen-2 0.00
- V68V (p.Val68Val), gnomAD 3-12381335-G-T, CADD 7.67
- D69Y (p.Asp69Tyr), gnomAD 3-12379907-G-T, CADD 24.70, PolyPhen-2 0.92
- D69N (p.Asp69Asn), rs181976291, gnomAD 3-12379907-G-A, CADD 22.20, PolyPhen-2 0.03
- D69D (p.Asp69Asp), rs753817211, gnomAD 3-12379909-C-T, CADD 9.66
- I73V (p.Ile73Val), rs1262418036, gnomAD 3-12381327-A-G, CADD 19.30, PolyPhen-2 0.04
- S74R (p.Ser74Arg), rs758581958, gnomAD 3-12379931-A-C, CADD 25.70, PolyPhen-2 0.11
- S74F (p.Ser74Phe), gnomAD 3-12381346-C-T, CADD 25.90, PolyPhen-2 1.00
- S74S (p.Ser74Ser), rs758183823, gnomAD 3-12381347-T-G, CADD 6.76
- S74A (p.Ser74Ala), rs755081984, gnomAD 3-12381360-T-G, CADD 18.30, PolyPhen-2 0.03
- H77N (p.His77Asn), gnomAD 3-12381390-C-A, CADD 17.90, PolyPhen-2 0.01
- H77Y (p.His77Tyr), gnomAD 3-12381390-C-T, CADD 15.70, PolyPhen-2 0.00
- H77H (p.His77His), rs749662645, gnomAD 3-12381392-T-C, CADD 0.69
- Y78H (p.Tyr78His), gnomAD 3-12379853-T-C, CADD 23.70, PolyPhen-2 0.95
- Y78C (p.Tyr78Cys), rs1286678629, gnomAD 3-12379854-A-G, CADD 24.40, PolyPhen-2 0.96
- Y78Y (p.Tyr78Tyr), rs769226133, gnomAD 3-12379855-C-T, CADD 2.25
- Y78F (p.Tyr78Phe), rs1183297709, gnomAD 3-12379899-A-T, CADD 22.00, PolyPhen-2 0.16
- Y78S (p.Tyr78Ser), gnomAD 3-12381355-A-C, CADD 22.20, PolyPhen-2 0.17
- E79* (p.Glu79Ter), NCI-TCGA Cosmic COSV5514, Variant assessed as somatic; high impact.
Public PPARG analysis runs
- PPARG analysis run — PPARG (403 variants) — completed 2026-08-18