IFNG (Interferon gamma) variants and mutations
IFNG (also known as Interferon gamma) is a human protein-coding gene encoding an interferon gamma protein. It activates macrophages, enhances antigen presentation, and coordinates cellular immunity against intracellular pathogens through STAT1-dependent transcription. Disruption of its signaling causes profound susceptibility to mycobacterial infection, while excessive production contributes to immune-mediated tissue injury. This analysis covers 473 IFNG variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes immunodeficiency 69, Primary hemophagocytic lymphohistiocytosis, and hemophagocytic syndrome. Example IFNG variants include K2T, K2K, and K2R.
Variant analysis overview
- Gene: IFNG
- Protein: Interferon gamma
- UniProt accession: P01579
- Organism: Homo sapiens
- Variants analyzed: 473
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 280 unspecified-consequence records; 1 stop retained variant; 84 synonymous variants; 83 missense variants; 2 in-frame deletions; 3 splice-region variants; 6 stop-gained variants; 11 frameshift variants; 3 substitution
- Prediction scores: 408 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: immunodeficiency 69, Primary hemophagocytic lymphohistiocytosis, hemophagocytic syndrome, HIV-1 infection, hypothyroidism, tuberous sclerosis, myxedema, macrophage activation syndrome, inflammatory bowel disease, ulcerative colitis, uterine corpus leiomyoma, digestive system disorder.
Protein structure and variant hotspots
- Protein features: 3 post-translational modification sites.
- 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 IFNG variants
Examples include K2T, K2K, K2R, K2I, K2*, K2E, Y3*, Y3C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K2T (p.Lys2Thr), ExAC rs768834812, TOPMed rs768834812, gnomAD rs768834812, REVEL 0.02, MetaLR 0.05
- K2K (p.Lys2Lys), gnomAD 12-68159610-T-C, CADD 0.31
- K2R (p.Lys2Arg), gnomAD 12-68159611-T-C, REVEL 0.05, MetaLR 0.06
- K2I (p.Lys2Ile), gnomAD 12-68159611-T-A, REVEL 0.03, MetaLR 0.08
- K2* (p.Lys2Ter), gnomAD 12-68159612-T-A, CADD 34.00
- K2E (p.Lys2Glu), gnomAD 12-68159612-T-C, REVEL 0.05, MetaLR 0.07
- Y3* (p.Tyr3Ter), rs1358756680, NCI-TCGA Cosmic COSV9997, gnomAD rs1358756680, Variant assessed as somatic; high impact.
- Y3C (p.Tyr3Cys), NCI-TCGA Cosmic COSV5749, Variant assessed as somatic; moderate impact.
- Y3H (p.Tyr3His), Ensembl rs1169058382
- Y3S (p.Tyr3Ser), TOPMed rs1882656272, MetaLR 0.07, MetaSVM -1.00
- Y3Y (p.Tyr3Tyr), gnomAD 12-68159607-A-G, CADD 0.04
- T4A (p.Thr4Ala), NCI-TCGA TCGA novel, REVEL 0.06, MetaLR 0.07, Variant assessed as somatic; moderate impact.
- T4I (p.Thr4Ile), ESP rs371849964, ExAC rs371849964, TOPMed rs371849964, gnomAD rs371849964, REVEL 0.12, MetaLR 0.21
- T4K (p.Thr4Lys), ESP rs371849964, ExAC rs371849964, TOPMed rs371849964, gnomAD rs371849964, REVEL 0.16, MetaLR 0.16
- T4T (p.Thr4Thr), gnomAD 12-68159604-T-G, CADD 4.50
- S5T (p.Ser5Thr), Ensembl rs563660500, MetaLR 0.04, MetaSVM -1.07
- S5S (p.Ser5Ser), gnomAD 12-68159601-A-G, CADD 3.23
- S5G (p.Ser5Gly), gnomAD 12-68159603-T-C, REVEL 0.02, MetaLR 0.05
- Y6C (p.Tyr6Cys), gnomAD rs1377379698, REVEL 0.04, MetaLR 0.04
- Y6H (p.Tyr6His), ExAC rs775727674, gnomAD rs775727674, REVEL 0.12, MetaLR 0.10
- Y6D (p.Tyr6Asp), gnomAD 12-68159600-A-C, REVEL 0.18, MetaLR 0.09
- I7T (p.Ile7Thr), Ensembl rs1882655944, REVEL 0.09, MetaLR 0.10
- I7I (p.Ile7Ile), rs1174419833, gnomAD 12-68159595-G-A, CADD 5.37
- I7V (p.Ile7Val), gnomAD 12-68159597-T-C, REVEL 0.04, MetaLR 0.05
- L8L (p.Leu8Leu), rs772210071, gnomAD 12-68159592-C-T, CADD 3.45
- L8S (p.Leu8Ser), gnomAD 12-68159593-A-G, REVEL 0.38, MetaLR 0.31
- A9S (p.Ala9Ser), Ensembl rs2120751320, REVEL 0.19, MetaLR 0.23
- A9A (p.Ala9Ala), gnomAD 12-68159589-A-G, CADD 8.37
- A9G (p.Ala9Gly), gnomAD 12-68159590-G-C, REVEL 0.16, MetaLR 0.19
- A9V (p.Ala9Val), gnomAD 12-68159590-G-A, REVEL 0.12, MetaLR 0.09
- A9D (p.Ala9Asp), gnomAD 12-68159590-G-T, REVEL 0.25, MetaLR 0.19
- A9P (p.Ala9Pro), gnomAD 12-68159591-C-G, REVEL 0.30, MetaLR 0.24
- Q11* (p.Gln11Ter), Ensembl rs2120751302, CADD 34.00
- Q11E (p.Gln11Glu), NCI-TCGA Cosmic COSV5749, Variant assessed as somatic; moderate impact.
- Q11H (p.Gln11His), NCI-TCGA TCGA novel, REVEL 0.18, MetaLR 0.21, Variant assessed as somatic; moderate impact.
- Q11R (p.Gln11Arg), gnomAD 12-68159584-T-C, REVEL 0.16, MetaLR 0.16
- Q11S (p.Gln11Ser), gnomAD 12-68159585-GA-G, CADD 5.21
- L12F (p.Leu12Phe), Ensembl rs2120751287
- L12L (p.Leu12Leu), gnomAD 12-68159580-G-C, CADD 2.40
- L12I (p.Leu12Ile), gnomAD 12-68159582-G-T, REVEL 0.16, MetaLR 0.19
- C13Y (p.Cys13Tyr), Ensembl rs2120751266, REVEL 0.14, MetaLR 0.07
- C13* (p.Cys13Ter), gnomAD 12-68159577-G-T, CADD 26.50
- C13F (p.Cys13Phe), gnomAD 12-68159578-C-A, REVEL 0.08, MetaLR 0.07
- C13R (p.Cys13Arg), gnomAD 12-68159579-A-G, REVEL 0.21, MetaLR 0.13
- I14V (p.Ile14Val), ExAC rs745621454, TOPMed rs745621454, gnomAD rs745621454, REVEL 0.00, MetaLR 0.03
- I14I (p.Ile14Ile), gnomAD 12-68159574-G-T, CADD 3.05
- V15A (p.Val15Ala), NCI-TCGA Cosmic COSV9997, MetaLR 0.12, MetaSVM -0.93, Variant assessed as somatic; moderate impact.
- V15F (p.Val15Phe), ExAC rs757239347, TOPMed rs757239347, gnomAD rs757239347, REVEL 0.11, MetaLR 0.10
- V15I (p.Val15Ile), rs757239347, NCI-TCGA Cosmic COSV5749, ExAC rs757239347, TOPMed rs757239347, REVEL 0.01, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- V15L (p.Val15Leu), ExAC rs757239347, TOPMed rs757239347, gnomAD rs757239347, REVEL 0.01, MetaLR 0.04
- V15V (p.Val15Val), gnomAD 12-68159571-A-G, CADD 1.24
- L16M (p.Leu16Met), ExAC rs749298180, TOPMed rs749298180, gnomAD rs749298180, REVEL 0.22, MetaLR 0.21, Uncertain significance, not specified
- L16F (p.Leu16Phe), gnomAD 12-68159568-C-A, REVEL 0.15, MetaLR 0.16
- L16W (p.Leu16Trp), rs2120751170, gnomAD 12-68159568-CA-C, CADD 19.10
- L16L (p.Leu16Leu), rs749298180, gnomAD 12-68159570-A-G, CADD 3.35
- G17C (p.Gly17Cys), Ensembl rs2120751162
- G17G (p.Gly17Gly), rs1206771822, gnomAD 12-68159565-A-G, CADD 2.34
- G17D (p.Gly17Asp), gnomAD 12-68159566-C-T, REVEL 0.14, MetaLR 0.13
- S18C (p.Ser18Cys), ExAC rs777144079, TOPMed rs777144079, gnomAD rs777144079
- S18F (p.Ser18Phe), ExAC rs777144079, TOPMed rs777144079, gnomAD rs777144079, REVEL 0.02, MetaLR 0.08
- S18Y (p.Ser18Tyr), rs777144079, ExAC rs777144079, TOPMed rs777144079, gnomAD rs777144079, REVEL 0.14, MetaLR 0.19, Variant assessed as somatic; moderate impact.
- G20D (p.Gly20Asp), Ensembl rs2120751114
- G20S (p.Gly20Ser), NCI-TCGA Cosmic COSV5749, REVEL 0.07, MetaLR 0.07, Variant assessed as somatic; moderate impact.
- G20V (p.Gly20Val), Ensembl rs2120751114, MetaLR 0.24, MetaSVM -0.88
- G20G (p.Gly20Gly), rs752160552, gnomAD 12-68159556-G-A, CADD 4.40
- G20C (p.Gly20Cys), gnomAD 12-68159558-C-A, REVEL 0.20, MetaLR 0.13
- C21R (p.Cys21Arg), Ensembl rs1882655203, REVEL 0.26, MetaLR 0.17
- C21Y (p.Cys21Tyr), Ensembl rs2120751090, REVEL 0.02, MetaLR 0.06
- C21C (p.Cys21Cys), gnomAD 12-68159553-A-G, CADD 2.23
- Y22Y (p.Tyr22Tyr), rs2120751082, gnomAD 12-68159550-G-A, CADD 2.11
- C23* (p.Cys23Ter), rs1325493656, NCI-TCGA Cosmic COSV9997, gnomAD rs1325493656, CADD 28.30, Variant assessed as somatic; high impact.
- C23Y (p.Cys23Tyr), Ensembl rs2120751075, REVEL 0.24, MetaLR 0.28
- C23C (p.Cys23Cys), rs1325493656, gnomAD 12-68159547-G-A, CADD 4.08
- C23R (p.Cys23Arg), gnomAD 12-68159549-A-G, REVEL 0.27, MetaLR 0.11
- Q24H (p.Gln24His), Ensembl rs2120751056
- Q24K (p.Gln24Lys), rs1284139476, gnomAD rs1284139476, AlphaMissense 0.08, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- Q24Q (p.Gln24Gln), gnomAD 12-68159544-C-T, CADD 3.11
- D25N (p.Asp25Asn), NCI-TCGA Cosmic COSV9997, MetaLR 0.07, MetaSVM -1.08, Variant assessed as somatic; moderate impact.
- D25D (p.Asp25Asp), rs1218296219, gnomAD 12-68159541-G-A, CADD 0.47
- D25E (p.Asp25Glu), gnomAD 12-68159541-G-T, REVEL 0.05, MetaLR 0.07
- P26A (p.Pro26Ala), Ensembl rs2120751043
- P26P (p.Pro26Pro), rs1338475508, gnomAD 12-68159538-T-C, CADD 2.15
- P26Q (p.Pro26Gln), gnomAD 12-68159539-G-T, REVEL 0.01, MetaLR 0.08
- Y27* (p.Tyr27Ter), gnomAD 12-68159535-A-T, CADD 31.00
- Y27Y (p.Tyr27Tyr), rs200003408, gnomAD 12-68159535-A-G, CADD 2.52
- Y27H (p.Tyr27His), gnomAD 12-68159537-A-G, REVEL 0.18, MetaLR 0.05
- V28A (p.Val28Ala), NCI-TCGA TCGA novel, REVEL 0.00, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- K29Q (p.Lys29Gln), UniProt VAR 004017
- K29R (p.Lys29Arg), Ensembl rs1882654801, MetaLR 0.13, MetaSVM -0.96
- K29K (p.Lys29Lys), rs1383213120, gnomAD 12-68159529-T-C, CADD 1.58
- K29E (p.Lys29Glu), gnomAD 12-68159531-T-C, REVEL 0.01, MetaLR 0.09
- E30E (p.Glu30Glu), rs1882654687, gnomAD 12-68159526-T-C, CADD 4.05
- E30K (p.Glu30Lys), gnomAD 12-68159528-CT-C, CADD 13.70
- A31T (p.Ala31Thr), gnomAD rs1238609496, REVEL 0.04, MetaLR 0.03
- A31V (p.Ala31Val), ExAC rs754616353, gnomAD rs754616353, REVEL 0.04, MetaLR 0.04
- A31A (p.Ala31Ala), gnomAD 12-68159523-T-C, CADD 7.05
- A31E (p.Ala31Glu), gnomAD 12-68159524-G-T, REVEL 0.12, MetaLR 0.04
- E32D (p.Glu32Asp), NCI-TCGA TCGA novel, MetaLR 0.14, MetaSVM -0.95, Variant assessed as somatic; moderate impact.
- E32K (p.Glu32Lys), gnomAD 12-68159522-C-T, REVEL 0.19, MetaLR 0.21
- E32* (p.Glu32Ter), gnomAD 12-68159522-C-A, CADD 26.40
- N33K (p.Asn33Lys), NCI-TCGA Cosmic COSV5749, REVEL 0.01, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- N33S (p.Asn33Ser), ExAC rs750753671, gnomAD rs750753671, REVEL 0.02, MetaLR 0.06
- N33D (p.Asn33Asp), gnomAD 12-68159519-T-C, REVEL 0.02, MetaLR 0.06
- L34I (p.Leu34Ile), Ensembl rs2120750958, REVEL 0.25, MetaLR 0.30
- L34L (p.Leu34Leu), gnomAD 12-68159514-A-T, CADD 0.41
- L34P (p.Leu34Pro), gnomAD 12-68159515-A-G, REVEL 0.43, MetaLR 0.43
- K35N (p.Lys35Asn), NCI-TCGA Cosmic COSV9997, REVEL 0.17, MetaLR 0.24, Variant assessed as somatic; moderate impact.
- K35R (p.Lys35Arg), gnomAD 12-68159512-T-C, REVEL 0.18, MetaLR 0.19
- K36N (p.Lys36Asn), gnomAD 12-68159508-T-G, REVEL 0.01, MetaLR 0.05
- K36K (p.Lys36Lys), rs765636767, gnomAD 12-68159508-T-C, CADD 2.46
- K36R (p.Lys36Arg), gnomAD 12-68159509-T-C, REVEL 0.02, MetaLR 0.07
- K36I (p.Lys36Ile), gnomAD 12-68159509-T-A, REVEL 0.03, MetaLR 0.11
- K36E (p.Lys36Glu), gnomAD 12-68159510-T-C, REVEL 0.03, MetaLR 0.04
- Y37C (p.Tyr37Cys), gnomAD rs1477303678, REVEL 0.52, MetaLR 0.39
- Y37H (p.Tyr37His), ExAC rs762291654, gnomAD rs762291654, REVEL 0.18, MetaLR 0.18
- F38C (p.Phe38Cys), NCI-TCGA Cosmic COSV5749, MetaLR 0.29, MetaSVM -0.49, Variant assessed as somatic; moderate impact.
- F38L (p.Phe38Leu), gnomAD 12-68159501-CA-C, CADD 34.00
- F38F (p.Phe38Phe), rs1420760098, gnomAD 12-68159502-A-G, CADD 16.00
- F38S (p.Phe38Ser), gnomAD 12-68159503-A-G, REVEL 0.33, MetaLR 0.24
- N39H (p.Asn39His), NCI-TCGA Cosmic COSV9997, Variant assessed as somatic; moderate impact.
- N39Y (p.Asn39Tyr), Ensembl rs2120746966, REVEL 0.34, MetaLR 0.28
- N39N (p.Asn39Asn), rs1309260379, gnomAD 12-68158257-A-G, CADD 2.07
- N39T (p.Asn39Thr), gnomAD 12-68158258-T-G, REVEL 0.32, MetaLR 0.26
- N39S (p.Asn39Ser), gnomAD 12-68158258-T-C, REVEL 0.29, MetaLR 0.19
- N39D (p.Asn39Asp), gnomAD 12-68158259-T-C, REVEL 0.21, MetaLR 0.16
- A40G (p.Ala40Gly), Ensembl rs2120746940, MetaLR 0.19, MetaSVM -0.84
- A40T (p.Ala40Thr), Ensembl rs2120746950, REVEL 0.17, MetaLR 0.17
- A40V (p.Ala40Val), Ensembl rs2120746940, REVEL 0.30, MetaLR 0.25
- A40A (p.Ala40Ala), rs1373222170, gnomAD 12-68158254-T-A, CADD 7.71
- A40E (p.Ala40Glu), gnomAD 12-68158255-G-T, REVEL 0.34, MetaLR 0.33
- A40S (p.Ala40Ser), gnomAD 12-68158256-C-A, REVEL 0.08, MetaLR 0.12
- A40P (p.Ala40Pro), gnomAD 12-68158256-C-G, REVEL 0.26, MetaLR 0.30
- G41A (p.Gly41Ala), gnomAD rs1337955616, MetaLR 0.04, MetaSVM -1.05
- G41C (p.Gly41Cys), ExAC rs762786646, gnomAD rs762786646, REVEL 0.04, MetaLR 0.06
- G41R (p.Gly41Arg), ExAC rs762786646, gnomAD rs762786646, REVEL 0.04, MetaLR 0.06
- G41S (p.Gly41Ser), ExAC rs762786646, gnomAD rs762786646, REVEL 0.05, MetaLR 0.02
- G41V (p.Gly41Val), gnomAD rs1337955616, REVEL 0.04, MetaLR 0.04
- G41G (p.Gly41Gly), rs1330436545, gnomAD 12-68158251-A-G, CADD 2.87
- G41D (p.Gly41Asp), gnomAD 12-68158252-C-T, REVEL 0.02, MetaLR 0.03
- H42D (p.His42Asp), Ensembl rs2120746889
- H42L (p.His42Leu), Ensembl rs2120746880
- H42N (p.His42Asn), Ensembl rs2120746889, REVEL 0.03, MetaLR 0.03
- H42Q (p.His42Gln), Ensembl rs2120746870, MetaLR 0.04, MetaSVM -1.08
- H42Y (p.His42Tyr), NCI-TCGA Cosmic COSV5749, REVEL 0.01, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- H42H (p.His42His), gnomAD 12-68158248-A-G, CADD 1.11
- H42R (p.His42Arg), gnomAD 12-68158249-T-C, REVEL 0.03, MetaLR 0.07
- S43* (p.Ser43Ter), Ensembl rs2120746849, CADD 23.50
- S43L (p.Ser43Leu), Ensembl rs2120746849, REVEL 0.14, MetaLR 0.15
- S43T (p.Ser43Thr), Ensembl rs2120746864
- S43S (p.Ser43Ser), rs2120746835, gnomAD 12-68158245-T-C, CADD 3.81
- D44G (p.Asp44Gly), Ensembl rs1882631408, REVEL 0.31, MetaLR 0.30
- D44H (p.Asp44His), Ensembl rs2120746816
- D44N (p.Asp44Asn), Ensembl rs2120746816
- D44Y (p.Asp44Tyr), NCI-TCGA Cosmic COSV9997, Ensembl rs2120746816, Variant assessed as somatic; moderate impact.
- D44E (p.Asp44Glu), gnomAD 12-68158242-A-C, REVEL 0.18, MetaLR 0.24
- V45E (p.Val45Glu), Ensembl rs1009245499
- V45I (p.Val45Ile), gnomAD rs1461185598, REVEL 0.16, MetaLR 0.21
- V45L (p.Val45Leu), gnomAD rs1461185598, REVEL 0.27, MetaLR 0.21
- V45A (p.Val45Ala), gnomAD 12-68158240-A-G, REVEL 0.30, MetaLR 0.30
- A46E (p.Ala46Glu), ExAC rs772911580, gnomAD rs772911580, REVEL 0.17, MetaLR 0.14
- A46G (p.Ala46Gly), ExAC rs772911580, gnomAD rs772911580
- A46S (p.Ala46Ser), Ensembl rs2120746774
- A46T (p.Ala46Thr), Ensembl rs2120746774
- A46V (p.Ala46Val), ExAC rs772911580, gnomAD rs772911580, REVEL 0.16, MetaLR 0.19
- A46A (p.Ala46Ala), gnomAD 12-68158236-C-G, CADD 0.10
- D47E (p.Asp47Glu), Ensembl rs1882631123
- D47H (p.Asp47His), Ensembl rs2120746722
- D47N (p.Asp47Asn), Ensembl rs2120746722
- D47V (p.Asp47Val), NCI-TCGA Cosmic COSV5749, Variant assessed as somatic; moderate impact.
- D47Y (p.Asp47Tyr), Ensembl rs2120746722
- D47D (p.Asp47Asp), rs1882631123, gnomAD 12-68158233-A-G, CADD 1.94
- N48K (p.Asn48Lys), NCI-TCGA Cosmic COSV9997, MetaLR 0.05, MetaSVM -1.04, Variant assessed as somatic; moderate impact.
- N48S (p.Asn48Ser), NCI-TCGA Cosmic COSV5749, REVEL 0.03, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- G49A (p.Gly49Ala), Ensembl rs2120746664
- G49E (p.Gly49Glu), Ensembl rs2120746664
- G49R (p.Gly49Arg), Ensembl rs2120746675
- G49V (p.Gly49Val), Ensembl rs2120746664, MetaLR 0.29, MetaSVM -0.81
- T50S (p.Thr50Ser), Ensembl rs2120746660, MetaLR 0.04, MetaSVM -1.01
- T50N (p.Thr50Asn), gnomAD 12-68158225-G-T, REVEL 0.02, MetaLR 0.06
- L51F (p.Leu51Phe), Ensembl rs2120746646, REVEL 0.35, MetaLR 0.35
Public IFNG analysis runs
- IFNG analysis run — IFNG (473 variants) — completed 2026-08-19