C3 (Complement C3) variants and mutations
C3 (also known as Complement C3) is a human protein-coding gene encoding a complement protein. It is cleaved during complement activation to generate C3a and C3b, which amplify inflammation, opsonize targets, and drive formation of downstream complement complexes. Deficiency causes severe susceptibility to bacterial infection, while dysregulated activation contributes to complement-mediated kidney and inflammatory diseases. This analysis covers 2,032 C3 variants and mutations. Of these, 72% have computational variant effect predictions. Disease context includes atypical hemolytic-uremic syndrome with C3 anomaly, complement component 3 deficiency, and age-related macular degeneration. Example C3 variants include G2E, G2R, and P3L.
Variant analysis overview
- Gene: C3
- Protein: Complement C3
- UniProt accession: P01024
- Organism: Homo sapiens
- Variants analyzed: 2032
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,827 unspecified-consequence records; 3 stop lost; 72 synonymous variants; 87 missense variants; 22 frameshift variants; 1 in-frame insertions; 5 in-frame deletions; 3 stop-gained variants; 5 splice-region variants; 7 substitution
- Prediction scores: 1,466 variants have prediction scores (72% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: atypical hemolytic-uremic syndrome with C3 anomaly, complement component 3 deficiency, age-related macular degeneration, complement 3 glomerulopathy, atypical hemolytic-uremic syndrome, macular degeneration, age related macular degeneration 9, retinal disorder, paroxysmal nocturnal hemoglobinuria, atrophic macular degeneration, degeneration of macula and posterior pole, COVID-19.
Protein structure and variant hotspots
- Protein features: 2 domains; 11 post-translational modification sites.
- Structural context: 379 variants have structural context.
- PTM context: 13 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, ClinGen, MaveDB, LitVar.
Notable C3 variants
Examples include G2E, G2R, P3L, P3S, T4N, G6C, P7L, P7S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2E (p.Gly2Glu), NCI-TCGA Cosmic COSV9983, REVEL 0.31, AlphaMissense 0.14, Variant assessed as somatic; moderate impact.
- G2R (p.Gly2Arg), ExAC rs778996328, gnomAD rs778996328, REVEL 0.31, CADD 19.30
- P3L (p.Pro3Leu), rs770131369, ClinGen CA304805661, ClinVar RCV003726958, TOPMed rs770131369, REVEL 0.12, AlphaMissense 0.08, Uncertain significance, not provided
- P3S (p.Pro3Ser), ExAC rs757609303, TOPMed rs757609303, gnomAD rs757609303, REVEL 0.10, CADD 9.98
- T4N (p.Thr4Asn), gnomAD rs1400705088, REVEL 0.15, CADD 5.71
- G6C (p.Gly6Cys), ExAC rs749647041, TOPMed rs749647041, gnomAD rs749647041, REVEL 0.33, CADD 22.90
- P7L (p.Pro7Leu), NCI-TCGA Cosmic COSV5556, Uncertain significance, Atypical hemolytic-uremic syndrome with C3 anomaly; Age related macular degenera
- P7S (p.Pro7Ser), rs998953544, ClinGen CA304805651, ClinVar RCV003731152, TOPMed rs998953544, REVEL 0.08, CADD 1.04, Uncertain significance, not provided
- S8C (p.Ser8Cys), gnomAD rs1412677663, REVEL 0.28, CADD 12.30, Uncertain significance, not provided
- L9P (p.Leu9Pro), rs138214338, ClinGen CA9129927, ClinVar RCV001092937, ClinVar RCV001133672, REVEL 0.54, CADD 22.60, Conflicting interpretations, Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 a
- L10M (p.Leu10Met), rs756577495, ClinGen CA9129926, ClinVar RCV001373123, ClinVar RCV002294456, REVEL 0.46, CADD 22.70, Uncertain significance, Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 a
- L12M (p.Leu12Met), gnomAD rs1362305907
- L14Q (p.Leu14Gln), TOPMed rs1968140026, REVEL 0.68, CADD 23.00
- T15I (p.Thr15Ile), TOPMed rs776845513, gnomAD rs776845513, REVEL 0.23, CADD 4.40, Uncertain significance
- T15S (p.Thr15Ser), rs776845513, ClinGen CA403646412, ClinVar RCV002948670, TOPMed rs776845513, REVEL 0.13, AlphaMissense 0.08, Uncertain significance, not provided
- H16Q (p.His16Gln), rs184455094, ClinGen CA9129922, ClinVar RCV001130718, ClinVar RCV001130719, REVEL 0.13, AlphaMissense 0.30, Conflicting interpretations, not provided; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement com
- L17P (p.Leu17Pro), Ensembl rs868462118, REVEL 0.53, CADD 19.00
- P18S (p.Pro18Ser), rs1200505625, ClinGen CA403646397, ClinVar RCV003830103, gnomAD rs1200505625, REVEL 0.21, CADD 18.70, Uncertain significance, not provided
- P18T (p.Pro18Thr), NCI-TCGA TCGA novel, REVEL 0.27, CADD 18.60, Variant assessed as somatic; moderate impact.
- L19P (p.Leu19Pro), gnomAD rs1238902793, REVEL 0.35, CADD 22.20, Uncertain significance, not provided
- G22W (p.Gly22Trp), ExAC rs765928197, gnomAD rs765928197, REVEL 0.54, CADD 23.20
- S23C (p.Ser23Cys), Ensembl rs1968139292
- S23I (p.Ser23Ile), Ensembl rs771249936, REVEL 0.16, CADD 5.70
- S23R (p.Ser23Arg), gnomAD rs1445790122, REVEL 0.13, CADD 1.12
- S23T (p.Ser23Thr), Ensembl rs771249936, REVEL 0.18, CADD 1.81
- P24H (p.Pro24His), 1000Genomes rs201572119, ExAC rs201572119, TOPMed rs201572119, gnomAD rs201572119, REVEL 0.51, CADD 24.30, Uncertain significance
- P24L (p.Pro24Leu), rs201572119, ClinGen CA9129920, ClinVar RCV002604140, 1000Genomes rs201572119, REVEL 0.66, CADD 24.20, Uncertain significance, not provided
- M25T (p.Met25Thr), gnomAD rs1334683171, REVEL 0.35, CADD 22.80
- Y26C (p.Tyr26Cys), gnomAD rs963344483, REVEL 0.25, AlphaMissense 0.13
- S27F (p.Ser27Phe), rs1306521442, NCI-TCGA Cosmic COSV5557, TOPMed rs1306521442, gnomAD rs1306521442, REVEL 0.19, AlphaMissense 0.49, Variant assessed as somatic; moderate impact.
- I28V (p.Ile28Val), rs2512272247, ClinGen CA403646328, ClinVar RCV003667621, REVEL 0.03, CADD 13.60, Uncertain significance, not provided
- I29T (p.Ile29Thr), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- I29V (p.Ile29Val), rs1420892330, ClinGen CA403646321, ClinVar RCV002038883, ClinVar RCV005017100, REVEL 0.13, CADD 19.40, Uncertain significance, Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 a
- T30A (p.Thr30Ala), rs2512272238, ClinGen CA403646313, ClinVar RCV003027640, REVEL 0.12, CADD 23.40, Uncertain significance, not provided
- P31L (p.Pro31Leu), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- N32I (p.Asn32Ile), rs755012704, ClinGen CA9129900, ClinVar RCV002634904, ClinVar RCV003308186, REVEL 0.60, CADD 24.80, Uncertain significance, not provided; Inborn genetic diseases
- N32T (p.Asn32Thr), ExAC rs755012704, TOPMed rs755012704, gnomAD rs755012704, REVEL 0.50, CADD 24.20, Uncertain significance
- L34M (p.Leu34Met), gnomAD rs1488306123, REVEL 0.15, CADD 21.90
- R35L (p.Arg35Leu), Ensembl rs1568229734, REVEL 0.32, CADD 25.20
- R35Q (p.Arg35Gln), NCI-TCGA TCGA novel, Ensembl rs1568229734, Variant assessed as somatic; moderate impact.
- R35W (p.Arg35Trp), rs1218842967, NCI-TCGA Cosmic COSV5557, gnomAD rs1218842967, REVEL 0.25, CADD 19.50, Variant assessed as somatic; moderate impact.
- E37G (p.Glu37Gly), ExAC rs760705687, gnomAD rs760705687, REVEL 0.29, AlphaMissense 0.09
- S38N (p.Ser38Asn), TOPMed rs1238527258, gnomAD rs1238527258, REVEL 0.06, CADD 7.07
- E39K (p.Glu39Lys), rs771084936, ClinGen CA9129895, NCI-TCGA Cosmic COSV5558, ClinVar RCV002607910, REVEL 0.20, AlphaMissense 0.14, Uncertain significance, not provided
- E40K (p.Glu40Lys), ExAC rs749382784, gnomAD rs749382784, REVEL 0.71, CADD 25.50
- E40V (p.Glu40Val), gnomAD rs1219352295, REVEL 0.76, CADD 26.80
- T41N (p.Thr41Asn), TOPMed rs1342405423, gnomAD rs1342405423, REVEL 0.30, CADD 6.03
- M42T (p.Met42Thr), ExAC rs773565405, gnomAD rs773565405
- M42V (p.Met42Val), Ensembl rs1968117728
- V43L (p.Val43Leu), NCI-TCGA TCGA novel, REVEL 0.12, CADD 11.10, Variant assessed as somatic; moderate impact.
- V43M (p.Val43Met), TOPMed rs1968117626, gnomAD rs1968117626, REVEL 0.36, CADD 14.50
- D48N (p.Asp48Asn), ESP rs141447426, ExAC rs141447426, TOPMed rs141447426, gnomAD rs141447426, REVEL 0.23, CADD 15.90, Uncertain significance, not provided
- A49E (p.Ala49Glu), TOPMed rs749153052, REVEL 0.07, CADD 0.00
- A49S (p.Ala49Ser), rs1599529587, ClinGen CA403646186, ClinVar RCV003388746, AlphaMissense 0.08, MetaLR 0.08, Uncertain significance, Atypical hemolytic-uremic syndrome with C3 anomaly
- A49T (p.Ala49Thr), NCI-TCGA Cosmic COSV5557, TOPMed rs1599529587, REVEL 0.12, AlphaMissense 0.08, Variant assessed as somatic; moderate impact.
- A49V (p.Ala49Val), TOPMed rs749153052, REVEL 0.03, CADD 0.00
- Q50E (p.Gln50Glu), rs780548430, ClinGen CA9129887, ClinVar RCV003841417, ExAC rs780548430, REVEL 0.06, CADD 0.01, Uncertain significance, not provided
- G51E (p.Gly51Glu), Ensembl rs866471464, REVEL 0.04, AlphaMissense 0.18
- G51R (p.Gly51Arg), TOPMed rs1370475575
- V53I (p.Val53Ile), NCI-TCGA TCGA novel, REVEL 0.03, CADD 0.01, Uncertain significance, not provided
- V55A (p.Val55Ala), rs1477866705, ClinGen CA403646134, ClinVar RCV003080109, gnomAD rs1477866705, REVEL 0.23, CADD 19.30, Uncertain significance, not provided
- T56A (p.Thr56Ala), rs2145438127, ClinGen CA403646128, ClinVar RCV001966831, Ensembl rs2145438127, AlphaMissense 0.09, MetaLR 0.08, Uncertain significance, not provided
- T56I (p.Thr56Ile), gnomAD rs1420958063, REVEL 0.08, AlphaMissense 0.08
- V57I (p.Val57Ile), gnomAD rs1477487433, REVEL 0.05, CADD 7.15
- V57L (p.Val57Leu), gnomAD rs1477487433, REVEL 0.07, CADD 13.40
- T58I (p.Thr58Ile), Ensembl rs1968116811
- V59A (p.Val59Ala), rs1568229666, ClinGen CA403646092, ClinVar RCV003731047, ClinVar RCV005014911, REVEL 0.37, CADD 24.70, Uncertain significance, not provided; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement com
- H60N (p.His60Asn), TOPMed rs1968116619
- H60Q (p.His60Gln), Ensembl rs1968116570
- D61E (p.Asp61Glu), TOPMed rs947639403, gnomAD rs947639403, REVEL 0.46, CADD 24.40
- D61N (p.Asp61Asn), rs778521833, ExAC rs778521833, TOPMed rs778521833, gnomAD rs778521833, REVEL 0.40, CADD 23.30, Uncertain significance, not specified; Atypical hemolytic-uremic syndrome
- D61D (p.Asp61Asp), rs780269222, gnomAD 19-6677957-G-A, CADD 0.40
- F62L (p.Phe62Leu), ESP rs368721587, TOPMed rs368721587
- P63S (p.Pro63Ser), rs2145438093, ClinGen CA403646042, ClinVar RCV001943937, Ensembl rs2145438093, AlphaMissense 0.46, MetaLR 0.76, Uncertain significance, not provided
- G64D (p.Gly64Asp), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- K65E (p.Lys65Glu), rs539992721, ClinGen CA403646023, ClinVar RCV003675054, ExAC rs539992721, AlphaMissense 0.28, MetaLR 0.65, Uncertain significance, not provided
- K65Q (p.Lys65Gln), rs539992721, ClinGen CA9129883, ClinVar RCV000427027, ClinVar RCV001328274, REVEL 0.67, AlphaMissense 0.28, Conflicting interpretations, not specified; not provided; Age related macular degeneration 9
- K66N (p.Lys66Asn), NCI-TCGA TCGA novel, TOPMed rs1968116239, Variant assessed as somatic; high impact.
- L67V (p.Leu67Val), TOPMed rs1968116196, Uncertain significance, Atypical hemolytic-uremic syndrome
- L69V (p.Leu69Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S70F (p.Ser70Phe), rs753544234, ExAC rs753544234, gnomAD rs753544234, AlphaMissense 0.13, MetaLR 0.18, Variant assessed as somatic; moderate impact.
- E72G (p.Glu72Gly), rs2512272081, ClinGen CA403645930, ClinVar RCV002705760, Uncertain significance, not provided
- T74N (p.Thr74Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L76V (p.Leu76Val), NCI-TCGA Cosmic COSV5557, Variant assessed as somatic; moderate impact.
- T77N (p.Thr77Asn), TOPMed rs1968115872, gnomAD rs1968115872, REVEL 0.19, CADD 1.58
- T77P (p.Thr77Pro), Ensembl rs1599529513
- A79S (p.Ala79Ser), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- A79T (p.Ala79Thr), gnomAD rs1445075668, REVEL 0.33, CADD 13.30
- N81D (p.Asn81Asp), ExAC rs767630028, TOPMed rs767630028, gnomAD rs767630028, REVEL 0.19, CADD 2.54
- N81S (p.Asn81Ser), rs2512272046, ClinGen CA403645794, ClinVar RCV003697678, Uncertain significance, not provided
- M83L (p.Met83Leu), Ensembl rs1599529503
- M83T (p.Met83Thr), gnomAD rs1332648857, REVEL 0.30, CADD 18.40
- G84S (p.Gly84Ser), rs1433338521, ClinGen CA403645738, ClinVar RCV003682235, gnomAD rs1433338521, REVEL 0.16, CADD 0.40, Uncertain significance, not provided
- V86F (p.Val86Phe), ExAC rs763113592, TOPMed rs763113592, gnomAD rs763113592, REVEL 0.13, CADD 10.80
- V86L (p.Val86Leu), ExAC rs763113592, TOPMed rs763113592, gnomAD rs763113592, REVEL 0.08, CADD 3.21
- T87P (p.Thr87Pro), Ensembl rs1599529491
- F88C (p.Phe88Cys), Ensembl rs2145438041
- F88L (p.Phe88Leu), Ensembl rs1968115196, REVEL 0.07, CADD 12.70, Uncertain significance, not provided
- T89K (p.Thr89Lys), ExAC rs770111904, gnomAD rs770111904, REVEL 0.17, CADD 0.48, Uncertain significance
- T89M (p.Thr89Met), rs770111904, ClinGen CA403645641, ClinVar RCV003549455, ExAC rs770111904, REVEL 0.18, CADD 11.60, Uncertain significance, not provided
- A92D (p.Ala92Asp), gnomAD rs1968089624, REVEL 0.20, CADD 19.00
- R94K (p.Arg94Lys), Ensembl rs1968089454, REVEL 0.01, CADD 2.06
- E95K (p.Glu95Lys), rs746332934, ClinGen CA9129850, ClinVar RCV002000946, ClinVar RCV002497964, REVEL 0.10, CADD 15.90, Uncertain significance, Inborn genetic diseases; Atypical hemolytic-uremic syndrome with C3 anomaly; Com
- K97M (p.Lys97Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E99V (p.Glu99Val), TOPMed rs1298387555, gnomAD rs1298387555, REVEL 0.03, AlphaMissense 0.13
- K100N (p.Lys100Asn), TOPMed rs1455156500, gnomAD rs1455156500, REVEL 0.04, CADD 10.10
- K100R (p.Lys100Arg), NCI-TCGA Cosmic COSV5557, Variant assessed as somatic; moderate impact.
- G101E (p.Gly101Glu), rs373754302, ClinGen CA9129849, ClinVar RCV003402702, ESP rs373754302, REVEL 0.05, CADD 6.98, Uncertain significance, C3-related disorder
- R102A (p.Arg102Ala), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; high impact., in allele C3F
- R102C (p.Arg102Cys), 1000Genomes rs2230199, ESP rs2230199, ExAC rs2230199, TOPMed rs2230199, REVEL 0.09, CADD 12.90, Benign, in allele C3F
- R102G (p.Arg102Gly), rs2512271118, ClinGen CA2697556137, ClinVar RCV003578778, REVEL 0.07, AlphaMissense 0.95, Uncertain significance, C3 glomerulonephritis; Atypical hemolytic-uremic syndrome; Complement component
- R102H (p.Arg102His), rs554587967, ClinGen CA9129848, ClinVar RCV001351670, ClinVar RCV002504563, REVEL 0.06, AlphaMissense 0.69, Uncertain significance, Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 a
- R102S (p.Arg102Ser), 1000Genomes rs2230199, ESP rs2230199, ExAC rs2230199, TOPMed rs2230199, REVEL 0.07, AlphaMissense 0.95, Benign, in allele C3F
- N103H (p.Asn103His), TOPMed rs1968088266
- K104E (p.Lys104Glu), rs1968088189, ClinGen CA403645284, ClinVar RCV003064538, ClinVar RCV005863795, REVEL 0.17, CADD 18.00, Uncertain significance, Atypical hemolytic-uremic syndrome; not provided
- F105L (p.Phe105Leu), rs2512271099, ClinGen CA403645272, ClinVar RCV003894112, ClinVar RCV006564446, REVEL 0.09, CADD 22.60, Uncertain significance, not provided
- V108M (p.Val108Met), rs747923416, ClinGen CA9129844, ClinVar RCV001029992, ClinVar RCV005021339, REVEL 0.17, CADD 21.00, Uncertain significance, Atypical hemolytic-uremic syndrome with C3 anomaly; Age related macular degenera
- Q109H (p.Gln109His), TOPMed rs957152531, gnomAD rs957152531, REVEL 0.06, AlphaMissense 0.23
- F112L (p.Phe112Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F112V (p.Phe112Val), Ensembl rs1968087711
- T114A (p.Thr114Ala), Ensembl rs774533380, REVEL 0.01, CADD 0.00
- T114I (p.Thr114Ile), rs552130054, ClinGen CA9129842, ClinVar RCV002614677, 1000Genomes rs552130054, REVEL 0.04, CADD 0.09, Uncertain significance, not provided
- T114N (p.Thr114Asn), 1000Genomes rs552130054, ExAC rs552130054, TOPMed rs552130054, gnomAD rs552130054, REVEL 0.01, CADD 0.01, Uncertain significance
- Q115K (p.Gln115Lys), TOPMed rs1968087411, gnomAD rs1968087411, REVEL 0.02, CADD 0.10
- V116M (p.Val116Met), rs2512271056, ClinGen CA403645208, ClinVar RCV003079227, Uncertain significance, not provided
- V120L (p.Val120Leu), Ensembl rs1968087337, REVEL 0.14, CADD 13.30
- V121L (p.Val121Leu), rs2145436858, ClinGen CA403645172, ClinVar RCV001949723, Ensembl rs2145436858, REVEL 0.20, CADD 16.60, Uncertain significance, not provided
- L122P (p.Leu122Pro), Ensembl rs768598098, REVEL 0.51, AlphaMissense 0.31, Uncertain significance
- L122R (p.Leu122Arg), rs768598098, ClinGen CA403645165, ClinVar RCV001977836, Ensembl rs768598098, AlphaMissense 0.31, MetaLR 0.28, Uncertain significance, not provided
- V123A (p.Val123Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V123F (p.Val123Phe), TOPMed rs1265210034, gnomAD rs1265210034, REVEL 0.28, AlphaMissense 0.25, Uncertain significance, Atypical hemolytic-uremic syndrome with C3 anomaly; Age related macular degenera
- V123I (p.Val123Ile), rs1265210034, ClinVar RCV004585826, AlphaMissense 0.25, MetaLR 0.06, Uncertain significance, not provided
- V123L (p.Val123Leu), TOPMed rs1265210034, gnomAD rs1265210034, REVEL 0.04, AlphaMissense 0.24, Uncertain significance, not provided
- S124G (p.Ser124Gly), TOPMed rs1047554865, gnomAD rs1047554865, REVEL 0.10, CADD 22.60
- S124N (p.Ser124Asn), rs201985442, ClinGen CA9129841, ClinVar RCV001910574, 1000Genomes rs201985442, REVEL 0.24, AlphaMissense 0.87, Uncertain significance, not provided
- Q126R (p.Gln126Arg), TOPMed rs1375858339
- S127R (p.Ser127Arg), Ensembl rs917865494, Likely benign
- G128R (p.Gly128Arg), TOPMed rs1968086495, REVEL 0.59, CADD 25.50
- Y129* (p.Tyr129Ter), rs2145436814, ClinGen CA403645119, ClinVar RCV002224681, ClinVar RCV005863670, CADD 36.00, Likely pathogenic
- L130V (p.Leu130Val), rs766237138, ClinGen CA9129840, ClinVar RCV002631208, ExAC rs766237138, REVEL 0.21, CADD 22.20, Uncertain significance, not provided
- F131L (p.Phe131Leu), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- T134A (p.Thr134Ala), ExAC rs753920167, TOPMed rs753920167, gnomAD rs753920167, REVEL 0.86, CADD 27.20, Uncertain significance, not provided
- D135G (p.Asp135Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K136R (p.Lys136Arg), TOPMed rs1968085893
- I138L (p.Ile138Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I138M (p.Ile138Met), NCI-TCGA Cosmic COSV5557, Variant assessed as somatic; moderate impact.
- T140N (p.Thr140Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T140P (p.Thr140Pro), Ensembl rs1599528602, REVEL 0.74, CADD 29.30
- T140S (p.Thr140Ser), NCI-TCGA Cosmic COSV5557, NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- G142D (p.Gly142Asp), gnomAD rs1458388275, REVEL 0.57, CADD 24.60
- G142R (p.Gly142Arg), NCI-TCGA Cosmic COSV5557, Variant assessed as somatic; moderate impact.
- S143A (p.Ser143Ala), ExAC rs775719070, gnomAD rs775719070, REVEL 0.36, CADD 20.50
- S143F (p.Ser143Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V145I (p.Val145Ile), rs199970572, ClinGen CA9129834, ClinVar RCV001957080, 1000Genomes rs199970572, REVEL 0.54, CADD 32.00, Uncertain significance, not provided
- L146I (p.Leu146Ile), NCI-TCGA Cosmic COSV9983, Variant assessed as somatic; moderate impact.
- Y147C (p.Tyr147Cys), gnomAD rs1199768689, REVEL 0.39, AlphaMissense 0.12
- Y147H (p.Tyr147His), ExAC rs767731378, gnomAD rs767731378, REVEL 0.48, CADD 22.80, Uncertain significance, not provided
- R148P (p.Arg148Pro), TOPMed rs886054657, gnomAD rs886054657, Uncertain significance
- R148Q (p.Arg148Gln), rs886054657, ClinGen CA10643358, ClinVar RCV000291131, ClinVar RCV000346017, REVEL 0.63, AlphaMissense 0.15, Uncertain significance, C3 glomerulonephritis; Complement component 3 deficiency; Age related macular de
- R148W (p.Arg148Trp), NCI-TCGA Cosmic COSV5557, REVEL 0.64, CADD 25.40, Uncertain significance, not provided
- T151I (p.Thr151Ile), NCI-TCGA Cosmic COSV5558, Variant assessed as somatic; moderate impact.
- T151S (p.Thr151Ser), rs1968082456, ClinGen CA403644968, ClinVar RCV001878434, ClinVar RCV002503393, REVEL 0.22, CADD 19.50, Uncertain significance, not specified; Age related macular degeneration 9; Complement component 3 defici
- V152I (p.Val152Ile), rs766880159, NCI-TCGA Cosmic COSV9983, ExAC rs766880159, TOPMed rs766880159, REVEL 0.30, CADD 10.40, Variant assessed as somatic; moderate impact.
- K155Q (p.Lys155Gln), rs147859257, ClinGen CA213419, ClinVar RCV000077796, ClinVar RCV000202831, REVEL 0.07, CADD 7.05, Conflicting interpretations, C3 glomerulonephritis; Complement component 3 deficiency; Atypical hemolytic-ure
- P158S (p.Pro158Ser), TOPMed rs1435501822
- V159E (p.Val159Glu), TOPMed rs1237755110, gnomAD rs1237755110, REVEL 0.45, CADD 23.00, Uncertain significance, Complement component 3 deficiency; C3 glomerulonephritis; Atypical hemolytic-ure
- V159L (p.Val159Leu), gnomAD rs1255051177, REVEL 0.09, CADD 13.50
- G160S (p.Gly160Ser), TOPMed rs1486448244, gnomAD rs1486448244, REVEL 0.06, CADD 13.80, Uncertain significance, Atypical hemolytic-uremic syndrome with C3 anomaly; Age related macular degenera
- R161G (p.Arg161Gly), rs776423109, ClinGen CA403644910, ClinVar RCV002726953, ExAC rs776423109, REVEL 0.31, CADD 24.10, Uncertain significance, not provided
- R161Q (p.Arg161Gln), Ensembl rs1968081043, REVEL 0.06, AlphaMissense 0.08
- R161W (p.Arg161Trp), rs776423109, ClinGen CA403644909, ClinVar RCV001507921, ClinVar RCV002466678, REVEL 0.53, CADD 24.40, Pathogenic/Likely pathogenic, not provided; Atypical hemolytic-uremic syndrome with C3 anomaly; C3 glomerulone
- T162R (p.Thr162Arg), rs2512270762, ClinGen CA403644901, ClinVar RCV003064537, ClinVar RCV005863794, Conflicting interpretations, Atypical hemolytic-uremic syndrome; not provided
- M164T (p.Met164Thr), ExAC rs746775340, gnomAD rs746775340, REVEL 0.14, CADD 14.40, Uncertain significance, not provided
- M164V (p.Met164Val), ExAC rs768476711, gnomAD rs768476711, REVEL 0.06, CADD 0.01
- V165A (p.Val165Ala), gnomAD rs1445999848, REVEL 0.38, CADD 23.00
- I167F (p.Ile167Phe), rs779750426, ClinGen CA9129806, ClinVar RCV002594244, ClinVar RCV005794356, REVEL 0.46, CADD 15.10, Uncertain significance, not provided; Inborn genetic diseases
- I167M (p.Ile167Met), TOPMed rs1330765911, gnomAD rs1330765911, REVEL 0.57, CADD 16.30
- P170L (p.Pro170Leu), rs771707355, NCI-TCGA Cosmic COSV9983, ExAC rs771707355, gnomAD rs771707355, REVEL 0.76, AlphaMissense 0.51, Uncertain significance
- P170R (p.Pro170Arg), rs771707355, ClinGen CA403643684, ClinVar RCV002017917, ExAC rs771707355, AlphaMissense 0.51, MetaLR 0.71, Uncertain significance, not provided
- P170S (p.Pro170Ser), Ensembl rs1967989449
Public C3 analysis runs
- C3 analysis run — C3 (2,032 variants) — completed 2026-08-19