PIK3CG (P48736) variants and mutations
PIK3CG (also known as P48736) is a human protein-coding gene encoding a phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform protein. Its annotated function is phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to…. It is annotated at the cytoplasm. This analysis covers 5,439 PIK3CG variants and mutations. Of these, 32% have computational variant effect predictions. Disease context includes B-cell chronic lymphocytic leukemia, immunodeficiency 72 with autoinflammation, and follicular lymphoma. Example PIK3CG variants include E2*, E2D, and E2G.
Variant analysis overview
- Gene: PIK3CG
- Protein: P48736
- UniProt accession: P48736
- Organism: Homo sapiens
- Variants analyzed: 5439
- Variant scope: all variants
- Completed: 2026-08-28
Variant and mutation evidence
- Variant composition: 5,170 unspecified-consequence records; 205 synonymous variants; 42 missense variants; 14 frameshift variants; 1 stop-gained variants; 6 in-frame deletions; 2 in-frame insertions; 1 protein altering variant; 2 substitution
- Prediction scores: 1,742 variants have prediction scores (32% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: B-cell chronic lymphocytic leukemia, immunodeficiency 72 with autoinflammation, follicular lymphoma, immunodeficiency 97 with autoinflammation, hypertensive disorder, neoplasm, essential hypertension, neoplasm of mature B-cells, breast cancer, lymphoma, cancer, kidney failure.
Protein structure and variant hotspots
- Protein features: 5 domains; 3 binding sites; 2 post-translational modification sites.
- Structural context: 4,030 variants have structural context.
- PTM context: 9 variants overlap post-translational modification sites.
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, MaveDB, LitVar.
Notable PIK3CG variants
Examples include E2*, E2D, E2G, E2K, E2Q, L3M, L3P, L3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2* (p.Glu2Ter), TOPMed rs777512949, gnomAD rs777512949, CADD 37.00
- E2D (p.Glu2Asp), Ensembl rs2116415672
- E2G (p.Glu2Gly), cosmic curated COSV10466, TOPMed rs1425001374, gnomAD rs1425001374, REVEL 0.10, MetaLR 0.26
- E2K (p.Glu2Lys), cosmic curated COSV63246, TOPMed rs777512949, gnomAD rs777512949
- E2Q (p.Glu2Gln), TOPMed rs777512949, gnomAD rs777512949, REVEL 0.11, MetaLR 0.27
- L3M (p.Leu3Met), gnomAD rs1165971751
- L3P (p.Leu3Pro), Ensembl rs1562952748, REVEL 0.17, MetaLR 0.21
- L3V (p.Leu3Val), gnomAD rs1165971751
- L3L (p.Leu3Leu), rs1165971751, gnomAD 7-106867568-C-T, CADD 9.34
- E4* (p.Glu4Ter), TOPMed rs1421718017, gnomAD rs1421718017
- E4D (p.Glu4Asp), cosmic curated COSV63253
- E4G (p.Glu4Gly), Ensembl rs2116415847, REVEL 0.07, MetaLR 0.20
- E4K (p.Glu4Lys), cosmic curated COSV63247, TOPMed rs1421718017, gnomAD rs1421718017, REVEL 0.07, MetaLR 0.27
- E4Q (p.Glu4Gln), TOPMed rs1421718017, gnomAD rs1421718017
- E4V (p.Glu4Val), Ensembl rs2116415847
- N5D (p.Asn5Asp), Ensembl rs2116415886, REVEL 0.09, MetaLR 0.08
- N5I (p.Asn5Ile), ExAC rs757965197, TOPMed rs757965197, gnomAD rs757965197
- N5K (p.Asn5Lys), Ensembl rs1584314207
- N5S (p.Asn5Ser), ExAC rs757965197, TOPMed rs757965197, gnomAD rs757965197
- N5T (p.Asn5Thr), ExAC rs757965197, TOPMed rs757965197, gnomAD rs757965197, REVEL 0.19, MetaLR 0.12, Uncertain significance, Inborn genetic diseases
- N5Y (p.Asn5Tyr), Ensembl rs2116415886
- Y6C (p.Tyr6Cys), rs757808746, NCI-TCGA Cosmic COSV6324, cosmic curated COSV63247, ExAC rs757808746, REVEL 0.20, MetaLR 0.17, Variant assessed as somatic; moderate impact.
- Y6F (p.Tyr6Phe), ExAC rs757808746, TOPMed rs757808746, gnomAD rs757808746
- Y6H (p.Tyr6His), 1000Genomes rs559570764, ExAC rs559570764, TOPMed rs559570764, gnomAD rs559570764, REVEL 0.09, MetaLR 0.11
- Y6N (p.Tyr6Asn), 1000Genomes rs559570764, ExAC rs559570764, TOPMed rs559570764, gnomAD rs559570764
- Y6Y (p.Tyr6Tyr), rs779358457, gnomAD 7-106867579-T-C, CADD 9.86
- K7* (p.Lys7Ter), Ensembl rs2116416025
- K7E (p.Lys7Glu), cosmic curated COSV63254
- K7I (p.Lys7Ile), Ensembl rs2116416054
- K7N (p.Lys7Asn), Ensembl rs2116416081
- K7R (p.Lys7Arg), Ensembl rs2116416054
- K7T (p.Lys7Thr), Ensembl rs2116416054
- K7Q (p.Lys7Gln), gnomAD 7-106867580-A-C, REVEL 0.13, MetaLR 0.15
- Q8* (p.Gln8Ter), Ensembl rs2116416119
- Q8E (p.Gln8Glu), Ensembl rs2116416119
- Q8H (p.Gln8His), Ensembl rs2116416191, REVEL 0.08, MetaLR 0.25
- Q8K (p.Gln8Lys), Ensembl rs2116416119, REVEL 0.13, MetaLR 0.25
- Q8L (p.Gln8Leu), Ensembl rs2116416154, REVEL 0.09, MetaLR 0.20
- Q8R (p.Gln8Arg), cosmic curated COSV10943, Ensembl rs2116416154
- Q8P (p.Gln8Pro), gnomAD 7-106867584-A-C, REVEL 0.12, MetaLR 0.15
- P9A (p.Pro9Ala), ExAC rs746307759, TOPMed rs746307759, gnomAD rs746307759
- P9H (p.Pro9His), TOPMed rs1199243117
- P9L (p.Pro9Leu), cosmic curated COSV10527, TOPMed rs1199243117, REVEL 0.12, MetaLR 0.20
- P9R (p.Pro9Arg), TOPMed rs1199243117
- P9S (p.Pro9Ser), ExAC rs746307759, TOPMed rs746307759, gnomAD rs746307759, REVEL 0.12, MetaLR 0.25
- P9T (p.Pro9Thr), ExAC rs746307759, TOPMed rs746307759, gnomAD rs746307759, REVEL 0.09, MetaLR 0.26
- P9P (p.Pro9Pro), rs772306261, gnomAD 7-106867588-C-G, CADD 0.91
- V10A (p.Val10Ala), rs927963993, NCI-TCGA Cosmic COSV6325, cosmic curated COSV63253, Ensembl rs927963993, AlphaMissense 0.14, MetaLR 0.26, Variant assessed as somatic; moderate impact.
- V10G (p.Val10Gly), Ensembl rs927963993
- V10L (p.Val10Leu), cosmic curated COSV63246, Ensembl rs2116416325, REVEL 0.09, MetaLR 0.24
- V10M (p.Val10Met), cosmic curated COSV63253, Ensembl rs2116416325, REVEL 0.13, MetaLR 0.28
- V10V (p.Val10Val), rs1371129587, gnomAD 7-106867591-G-A, CADD 8.97
- V11A (p.Val11Ala), gnomAD rs1273593548
- V11E (p.Val11Glu), gnomAD rs1273593548
- V11G (p.Val11Gly), cosmic curated COSV63246, gnomAD rs1273593548, REVEL 0.16, MetaLR 0.34
- V11L (p.Val11Leu), ExAC rs747163273, TOPMed rs747163273, gnomAD rs747163273
- V11M (p.Val11Met), cosmic curated COSV63251, ExAC rs747163273, TOPMed rs747163273, gnomAD rs747163273, REVEL 0.12, MetaLR 0.21
- V11V (p.Val11Val), rs1790334608, gnomAD 7-106867594-G-A, CADD 6.67
- L12M (p.Leu12Met), cosmic curated COSV63246, gnomAD rs1333618125
- L12P (p.Leu12Pro), ESP rs376062046, TOPMed rs376062046
- L12V (p.Leu12Val), gnomAD rs1333618125
- L12L (p.Leu12Leu), rs1333618125, gnomAD 7-106867595-C-T, CADD 9.86
- R13* (p.Arg13Ter), TOPMed rs1790335406
- R13G (p.Arg13Gly), TOPMed rs1790335406
- R13I (p.Arg13Ile), ExAC rs777538453, TOPMed rs777538453, gnomAD rs777538453, REVEL 0.40, MetaLR 0.25
- R13K (p.Arg13Lys), ExAC rs777538453, TOPMed rs777538453, gnomAD rs777538453, REVEL 0.18, MetaLR 0.28
- R13T (p.Arg13Thr), ExAC rs777538453, TOPMed rs777538453, gnomAD rs777538453
- R13S (p.Arg13Ser), gnomAD 7-106867600-A-C, REVEL 0.29, MetaLR 0.24
- E14* (p.Glu14Ter), NCI-TCGA TCGA novel, Ensembl rs1584314339, CADD 37.00, Variant assessed as somatic; high impact.
- E14D (p.Glu14Asp), 1000Genomes rs201564718, ExAC rs201564718, gnomAD rs201564718
- E14G (p.Glu14Gly), Ensembl rs2116416733
- E14K (p.Glu14Lys), cosmic curated COSV10527, Ensembl rs1584314339, REVEL 0.11, MetaLR 0.31
- E14Q (p.Glu14Gln), Ensembl rs1584314339, REVEL 0.19, MetaLR 0.33
- E14V (p.Glu14Val), Ensembl rs2116416733
- E14T (p.Glu14Thr), rs771137585, gnomAD 7-106867596-TGAGA, CADD 28.00
- E14E (p.Glu14Glu), rs201564718, gnomAD 7-106867603-G-A, CADD 8.59
- D15A (p.Asp15Ala), TOPMed rs1404417772, gnomAD rs1404417772
- D15E (p.Asp15Glu), Ensembl rs2116416880, REVEL 0.12, MetaLR 0.12
- D15G (p.Asp15Gly), TOPMed rs1404417772, gnomAD rs1404417772
- D15H (p.Asp15His), ExAC rs761955149, TOPMed rs761955149, gnomAD rs761955149
- D15N (p.Asp15Asn), ExAC rs761955149, TOPMed rs761955149, gnomAD rs761955149, REVEL 0.22, MetaLR 0.29
- D15V (p.Asp15Val), TOPMed rs1404417772, gnomAD rs1404417772, REVEL 0.21, MetaLR 0.22
- D15Y (p.Asp15Tyr), cosmic curated COSV63253, ExAC rs761955149, TOPMed rs761955149, gnomAD rs761955149, REVEL 0.27, MetaLR 0.36
- N16D (p.Asn16Asp), ESP rs145459032, ExAC rs145459032, TOPMed rs145459032, gnomAD rs145459032, REVEL 0.16, MetaLR 0.18
- N16H (p.Asn16His), ESP rs145459032, ExAC rs145459032, TOPMed rs145459032, gnomAD rs145459032, REVEL 0.10, MetaLR 0.15
- N16I (p.Asn16Ile), Ensembl rs1584314379
- N16K (p.Asn16Lys), gnomAD rs1231633674, REVEL 0.08, MetaLR 0.23
- N16S (p.Asn16Ser), Ensembl rs1584314379
- N16T (p.Asn16Thr), Ensembl rs1584314379
- N16Y (p.Asn16Tyr), ESP rs145459032, ExAC rs145459032, TOPMed rs145459032, gnomAD rs145459032
- C17* (p.Cys17Ter), 1000Genomes rs3729673, ESP rs3729673, ExAC rs3729673, TOPMed rs3729673, CADD 25.30
- C17G (p.Cys17Gly), TOPMed rs952660801, REVEL 0.10, MetaLR 0.10
- C17R (p.Cys17Arg), TOPMed rs952660801, REVEL 0.07, MetaLR 0.07
- C17S (p.Cys17Ser), TOPMed rs952660801
- C17W (p.Cys17Trp), 1000Genomes rs3729673, ESP rs3729673, ExAC rs3729673, TOPMed rs3729673
- C17Y (p.Cys17Tyr), ExAC rs773009910, gnomAD rs773009910, REVEL 0.08, MetaLR 0.13
- C17C (p.Cys17Cys), rs3729673, gnomAD 7-106867612-C-T, CADD 2.35
- R18* (p.Arg18Ter), cosmic curated COSV63248, gnomAD rs1417582796, CADD 34.00
- R18G (p.Arg18Gly), gnomAD rs1417582796
- R18L (p.Arg18Leu), 1000Genomes rs142380460, ExAC rs142380460, TOPMed rs142380460, gnomAD rs142380460, REVEL 0.18, MetaLR 0.32
- R18P (p.Arg18Pro), 1000Genomes rs142380460, ExAC rs142380460, TOPMed rs142380460, gnomAD rs142380460, REVEL 0.28, MetaLR 0.34
- R18Q (p.Arg18Gln), rs142380460, NCI-TCGA Cosmic COSV6324, cosmic curated COSV63248, 1000Genomes rs142380460, REVEL 0.14, MetaLR 0.31, Variant assessed as somatic; moderate impact.
- R18R (p.Arg18Arg), rs1417582796, gnomAD 7-106867613-C-A, CADD 7.02
- R19G (p.Arg19Gly), ExAC rs759138938, gnomAD rs759138938
- R19K (p.Arg19Lys), rs767132637, ClinGen CA4429071, ClinVar RCV002752136, ExAC rs767132637, REVEL 0.24, MetaLR 0.46, Uncertain significance, Inborn genetic diseases
- R19M (p.Arg19Met), ExAC rs767132637, TOPMed rs767132637, gnomAD rs767132637, Uncertain significance
- R19S (p.Arg19Ser), gnomAD rs1409409082
- R19T (p.Arg19Thr), ExAC rs767132637, TOPMed rs767132637, gnomAD rs767132637, Uncertain significance
- R19W (p.Arg19Trp), ExAC rs759138938, gnomAD rs759138938, REVEL 0.42, MetaLR 0.45
- R19R (p.Arg19Arg), rs1409409082, gnomAD 7-106867618-G-A, CADD 8.42
- R20C (p.Arg20Cys), NCI-TCGA Cosmic COSV6324, cosmic curated COSV63245, Ensembl rs2116417261, REVEL 0.34, MetaLR 0.47, Variant assessed as somatic; moderate impact.
- R20G (p.Arg20Gly), Ensembl rs2116417261
- R20H (p.Arg20His), rs1326957848, NCI-TCGA Cosmic COSV6324, cosmic curated COSV63245, gnomAD rs1326957848, REVEL 0.34, MetaLR 0.52, Variant assessed as somatic; moderate impact.
- R20L (p.Arg20Leu), gnomAD rs1326957848
- R20P (p.Arg20Pro), gnomAD rs1326957848
- R20S (p.Arg20Ser), Ensembl rs2116417261
- R20R (p.Arg20Arg), rs2116417318, gnomAD 7-106867621-C-A, CADD 7.36
- R21G (p.Arg21Gly), cosmic curated COSV10745, ExAC rs771734598, TOPMed rs771734598, gnomAD rs771734598, REVEL 0.16, MetaLR 0.25
- R21L (p.Arg21Leu), ExAC rs755613711, TOPMed rs755613711, gnomAD rs755613711
- R21P (p.Arg21Pro), ExAC rs755613711, TOPMed rs755613711, gnomAD rs755613711
- R21Q (p.Arg21Gln), ExAC rs755613711, TOPMed rs755613711, gnomAD rs755613711, REVEL 0.22, MetaLR 0.29
- R21W (p.Arg21Trp), cosmic curated COSV63248, ExAC rs771734598, TOPMed rs771734598, gnomAD rs771734598, REVEL 0.35, MetaLR 0.36
- R21R (p.Arg21Arg), rs2116417414, gnomAD 7-106867624-G-A, CADD 6.98
- R22G (p.Arg22Gly), Ensembl rs2116417443
- R22K (p.Arg22Lys), gnomAD rs1293906030, REVEL 0.14, MetaLR 0.22
- R22M (p.Arg22Met), cosmic curated COSV63251, gnomAD rs1293906030
- R22S (p.Arg22Ser), Ensembl rs547403667
- R22T (p.Arg22Thr), gnomAD rs1293906030
- R22W (p.Arg22Trp), Ensembl rs2116417443
- R22R (p.Arg22Arg), gnomAD 7-106867625-A-C, CADD 12.10
- M23I (p.Met23Ile), Ensembl rs893866491, cosmic curated COSV63247, REVEL 0.24, MetaLR 0.26
- M23K (p.Met23Lys), ExAC rs779528508, gnomAD rs779528508
- M23L (p.Met23Leu), Ensembl rs2116417546
- M23R (p.Met23Arg), ExAC rs779528508, gnomAD rs779528508
- M23V (p.Met23Val), Ensembl rs2116417546
- K24* (p.Lys24Ter), Ensembl rs2116417621
- K24E (p.Lys24Glu), Ensembl rs2116417621
- K24M (p.Lys24Met), Ensembl rs2116417652
- K24N (p.Lys24Asn), cosmic curated COSV10527, Ensembl rs1584314486
- K24R (p.Lys24Arg), Ensembl rs2116417652
- K24K (p.Lys24Lys), rs1584314486, gnomAD 7-106867633-G-A, CADD 8.48
- P25A (p.Pro25Ala), Ensembl rs2116417705
- P25L (p.Pro25Leu), ExAC rs750834144, gnomAD rs750834144, REVEL 0.10, MetaLR 0.26
- P25Q (p.Pro25Gln), ExAC rs750834144, gnomAD rs750834144
- P25R (p.Pro25Arg), ExAC rs750834144, gnomAD rs750834144, REVEL 0.08, MetaLR 0.26
- P25S (p.Pro25Ser), cosmic curated COSV63249, Ensembl rs2116417705, MetaLR 0.24, MetaSVM -0.61
- P25T (p.Pro25Thr), Ensembl rs2116417705, REVEL 0.09, MetaLR 0.24
- P25P (p.Pro25Pro), rs1279668366, gnomAD 7-106867636-G-A, CADD 1.32
- R26C (p.Arg26Cys), NCI-TCGA Cosmic COSV6324, cosmic curated COSV63247, TOPMed rs1790340029, REVEL 0.12, MetaLR 0.18, Variant assessed as somatic; moderate impact.
- R26G (p.Arg26Gly), TOPMed rs1790340029, REVEL 0.09, MetaLR 0.18
- R26H (p.Arg26His), rs1339698935, NCI-TCGA Cosmic COSV6324, cosmic curated COSV63249, TOPMed rs1339698935, REVEL 0.10, MetaLR 0.09, Variant assessed as somatic; moderate impact.
- R26L (p.Arg26Leu), TOPMed rs1339698935, gnomAD rs1339698935, REVEL 0.10, MetaLR 0.13
- R26P (p.Arg26Pro), TOPMed rs1339698935, gnomAD rs1339698935
- R26R (p.Arg26Arg), rs758833293, gnomAD 7-106867639-C-G, CADD 8.90
- S27C (p.Ser27Cys), Ensembl rs2116417875
- S27G (p.Ser27Gly), Ensembl rs2116417875
- S27N (p.Ser27Asn), gnomAD rs1270295206
- S27R (p.Ser27Arg), Ensembl rs2116417937
- S27T (p.Ser27Thr), gnomAD rs1270295206
- A28D (p.Ala28Asp), gnomAD rs1341469233, REVEL 0.13, MetaLR 0.24
- A28G (p.Ala28Gly), gnomAD rs1341469233
- A28P (p.Ala28Pro), Ensembl rs1790340790
- A28S (p.Ala28Ser), Ensembl rs1790340790, REVEL 0.10, MetaLR 0.10
- A28T (p.Ala28Thr), Ensembl rs1790340790, REVEL 0.08, MetaLR 0.10
- A28V (p.Ala28Val), NCI-TCGA TCGA novel, gnomAD rs1341469233, Variant assessed as somatic; moderate impact.
- A28C (p.Ala28Cys), gnomAD 7-106867640-AGT-A, CADD 24.90
- A28A (p.Ala28Ala), rs1790341108, gnomAD 7-106867645-T-G, CADD 0.58
- A29E (p.Ala29Glu), NCI-TCGA Cosmic COSV1007, Ensembl rs1790341417, REVEL 0.04, MetaLR 0.21, Variant assessed as somatic; moderate impact.
- A29G (p.Ala29Gly), Ensembl rs1790341417, REVEL 0.07, MetaLR 0.18
- A29P (p.Ala29Pro), TOPMed rs1790341270, REVEL 0.09, MetaLR 0.14, Uncertain significance, Inborn genetic diseases
- A29T (p.Ala29Thr), TOPMed rs1790341270, REVEL 0.05, MetaLR 0.14, Uncertain significance
- A29V (p.Ala29Val), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10078, Ensembl rs1790341417, REVEL 0.04, MetaLR 0.21, Uncertain significance, Inborn genetic diseases
- A29A (p.Ala29Ala), rs780581522, gnomAD 7-106867648-G-C, CADD 1.40
- A30D (p.Ala30Asp), 1000Genomes rs61757719, ExAC rs61757719, TOPMed rs61757719, gnomAD rs61757719, REVEL 0.11, MetaLR 0.18
- A30G (p.Ala30Gly), 1000Genomes rs61757719, ExAC rs61757719, TOPMed rs61757719, gnomAD rs61757719, REVEL 0.12, MetaLR 0.09
- A30P (p.Ala30Pro), NCI-TCGA TCGA novel, TOPMed rs1212203463, gnomAD rs1212203463, Variant assessed as somatic; moderate impact.
- A30S (p.Ala30Ser), TOPMed rs1212203463, gnomAD rs1212203463
- A30T (p.Ala30Thr), cosmic curated COSV10820, TOPMed rs1212203463, gnomAD rs1212203463, REVEL 0.17, MetaLR 0.12
- A30V (p.Ala30Val), cosmic curated COSV63246, 1000Genomes rs61757719, ExAC rs61757719, TOPMed rs61757719
- A30A (p.Ala30Ala), rs781560999, gnomAD 7-106867651-C-T, CADD 8.37
Public PIK3CG analysis runs
- PIK3CG analysis run — PIK3CG (5,439 variants) — completed 2026-08-28