TNFRSF1A (P19438) variants and mutations
TNFRSF1A (also known as P19438) is a human protein-coding gene encoding a tumor necrosis factor receptor superfamily member 1A protein. It mediates many inflammatory and cell-death responses to TNF through NF-kappaB, MAPK, and death-domain signaling. Dominant pathogenic variants that alter receptor handling cause TNF receptor-associated periodic syndrome, an inherited autoinflammatory disease. This analysis covers 973 TNFRSF1A variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes TNF receptor 1-associated periodic fever syndrome, Tumor necrosis factor receptor 1 associated periodic syndrome, and multiple sclerosis. Example TNFRSF1A variants include L3F, S4F, and T5N.
Variant analysis overview
- Gene: TNFRSF1A
- Protein: P19438
- UniProt accession: P19438
- Organism: Homo sapiens
- Variants analyzed: 973
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 595 unspecified-consequence records; 3 stop lost; 1 stop retained variant; 220 missense variants; 125 synonymous variants; 4 frameshift variants; 12 stop-gained variants; 5 in-frame deletions; 1 in-frame insertions; 7 substitution
- Prediction scores: 833 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: TNF receptor 1-associated periodic fever syndrome, Tumor necrosis factor receptor 1 associated periodic syndrome, multiple sclerosis, primary biliary cholangitis, Behcet disease, ankylosing spondylitis, autoinflammatory syndrome, hereditary disease, pneumonia, biliary liver cirrhosis, sclerosing cholangitis, psoriasis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 4 post-translational modification sites.
- Structural context: 353 variants have structural context.
- PTM context: 8 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 TNFRSF1A variants
Examples include L3F, S4F, T5N, T5P, V6M, P7A, P7T, D8A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- L3F (p.Leu3Phe), Ensembl rs951530289
- S4F (p.Ser4Phe), rs200593961, ClinGen CA6405647, ClinVar RCV001343900, ExAC rs200593961, REVEL 0.54, CADD 24.60, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- T5N (p.Thr5Asn), rs1948198919, ClinGen CA383551758, ClinVar RCV001229810, Ensembl rs1948198919, REVEL 0.50, CADD 23.30, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- T5P (p.Thr5Pro), Ensembl rs1592053709
- V6M (p.Val6Met), rs772424047, ClinGen CA6405644, ClinVar RCV000657858, ClinVar RCV001855361, REVEL 0.49, CADD 24.00, Conflicting interpretations, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- P7A (p.Pro7Ala), ExAC rs200727600, TOPMed rs200727600, gnomAD rs200727600, REVEL 0.64, CADD 22.20
- P7T (p.Pro7Thr), ExAC rs200727600, TOPMed rs200727600, gnomAD rs200727600, REVEL 0.57, CADD 22.40
- D8A (p.Asp8Ala), Ensembl rs1592053686, REVEL 0.54, CADD 23.30
- D8E (p.Asp8Glu), TOPMed rs1243050864, REVEL 0.50, CADD 23.70
- D8N (p.Asp8Asn), Ensembl rs2136835140
- L10M (p.Leu10Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P12L (p.Pro12Leu), Ensembl rs1555109224, REVEL 0.59, CADD 24.90
- P12R (p.Pro12Arg), rs939402192, []
- L13P (p.Leu13Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L15V (p.Leu15Val), gnomAD rs1434421197, REVEL 0.61, CADD 21.50
- L16P (p.Leu16Pro), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99369, Variant assessed as somatic; moderate impact.
- E17K (p.Glu17Lys), rs1948090517, ClinGen CA383551281, cosmic curated COSV99369, ClinVar RCV001990221, REVEL 0.44, CADD 16.20, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- V20A (p.Val20Ala), rs1254356365, ClinGen CA383551245, ClinVar RCV001937723, TOPMed rs1254356365, REVEL 0.59, CADD 15.40, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- V20M (p.Val20Met), rs2497801546, ClinGen CA383551250, ClinVar RCV003624878, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- G21A (p.Gly21Ala), rs1180778404, ClinGen CA383551234, ClinVar RCV001937507, TOPMed rs1180778404, REVEL 0.49, CADD 10.60, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y23C (p.Tyr23Cys), NCI-TCGA Cosmic COSV5083, cosmic curated COSV50830, Variant assessed as somatic; moderate impact.
- P24H (p.Pro24His), rs2497801506, ClinGen CA383551199, ClinVar RCV003512950, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- S25* (p.Ser25Ter), NCI-TCGA Cosmic COSV5082, cosmic curated COSV50829, Variant assessed as somatic; high impact.
- S25L (p.Ser25Leu), NCI-TCGA Cosmic COSV5082, cosmic curated COSV50827, Ensembl rs1948089967, REVEL 0.46, CADD 15.00, Variant assessed as somatic; moderate impact.
- G26A (p.Gly26Ala), gnomAD rs1259443563, REVEL 0.55, CADD 14.90
- V27D (p.Val27Asp), rs753595201, ClinGen CA6405611, ClinVar RCV001299665, ExAC rs753595201, REVEL 0.55, CADD 23.50, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- V27I (p.Val27Ile), TOPMed rs1182623871, gnomAD rs1182623871, REVEL 0.49, CADD 22.50
- I28F (p.Ile28Phe), gnomAD rs1469599003, REVEL 0.41, CADD 4.36
- L30M (p.Leu30Met), TOPMed rs1471642877
- L30V (p.Leu30Val), TOPMed rs1471642877
- V31G (p.Val31Gly), rs763940329, ClinGen CA6405610, ClinVar RCV000506549, ClinVar RCV001857279, REVEL 0.68, CADD 24.30, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS); not specified
- P32H (p.Pro32His), NCI-TCGA Cosmic COSV5082, cosmic curated COSV50828, Variant assessed as somatic; moderate impact.
- P32R (p.Pro32Arg), rs1592048275, ClinGen CA383551126, ClinVar RCV000796810, Ensembl rs1592048275, AlphaMissense 0.16, MetaLR 0.95, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- H33Q (p.His33Gln), TOPMed rs200063423, gnomAD rs200063423
- H33Y (p.His33Tyr), rs1005685583, NCI-TCGA Cosmic COSV9936, cosmic curated COSV99369, Ensembl rs1005685583, REVEL 0.48, CADD 13.20, Variant assessed as somatic; moderate impact.
- L34I (p.Leu34Ile), Ensembl rs906014003
- G35E (p.Gly35Glu), Ensembl rs201793570
- G35R (p.Gly35Arg), rs116336305, 1000Genomes rs116336305, ExAC rs116336305, gnomAD rs116336305, REVEL 0.47, CADD 0.84, Variant assessed as somatic; moderate impact.
- D36G (p.Asp36Gly), gnomAD rs1948089106, REVEL 0.63, CADD 22.20
- D36H (p.Asp36His), TOPMed rs1469655659, gnomAD rs1469655659, REVEL 0.65, CADD 12.80
- D36N (p.Asp36Asn), TOPMed rs1469655659, gnomAD rs1469655659, REVEL 0.44, CADD 13.10
- R37W (p.Arg37Trp), rs2136823158, ClinGen CA383551086, ClinVar RCV001884989, Ensembl rs2136823158, AlphaMissense 0.16, MetaLR 0.90, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- E38Q (p.Glu38Gln), rs2497801346, ClinGen CA383551076, ClinVar RCV003141053, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- D41E (p.Asp41Glu), rs104895271, ClinGen CA280695, ClinVar RCV000083896, ClinVar RCV000255687, REVEL 0.54, CADD 0.20, Pathogenic/Likely pathogenic, Autoinflammatory syndrome; Inborn genetic diseases; not provided
- D41H (p.Asp41His), rs199882512, ClinGen CA6405607, ClinVar RCV000658632, ClinVar RCV001376777, REVEL 0.55, CADD 24.50, Conflicting interpretations, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- D41V (p.Asp41Val), rs2136823142, ClinGen CA383551036, ClinVar RCV001509418, Ensembl rs2136823142, AlphaMissense 0.24, MetaLR 0.89, Uncertain significance, not provided
- S42N (p.Ser42Asn), TOPMed rs200140274, gnomAD rs200140274, Uncertain significance
- S42R (p.Ser42Arg), Ensembl rs201769520
- S42T (p.Ser42Thr), rs200140274, ClinGen CA232330910, ClinVar RCV003024163, TOPMed rs200140274, REVEL 0.61, CADD 0.69, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y49D (p.Tyr49Asp), rs104895237, ClinGen CA280701, ClinVar RCV000083898, Ensembl rs104895237, AlphaMissense 0.94, MetaLR 0.93, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y49H (p.Tyr49His), rs104895237, ClinGen CA280698, ClinVar RCV000083897, Ensembl rs104895237, AlphaMissense 0.94, MetaLR 0.93, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- I50V (p.Ile50Val), ExAC rs763595386, gnomAD rs763595386
- H51Q (p.His51Gln), rs104895254, ClinGen CA280710, ClinVar RCV000083901, UniProt VAR 019329, AlphaMissense 0.94, MetaLR 0.77, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- H51R (p.His51Arg), rs104895289, ClinGen CA280707, ClinVar RCV000083900, ClinVar RCV004589549, AlphaMissense 0.91, MetaLR 0.80, Uncertain significance, not provided
- H51Y (p.His51Tyr), rs104895227, ClinGen CA280704, ClinVar RCV000083899, ClinVar RCV001701502, AlphaMissense 0.53, MetaLR 0.83, Pathogenic, not provided
- N54I (p.Asn54Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S56L (p.Ser56Leu), rs199961053, ClinGen CA6405601, NCI-TCGA Cosmic COSV5082, cosmic curated COSV50828, REVEL 0.58, CADD 25.20, Uncertain significance, Inborn genetic diseases; TNF receptor-associated periodic fever syndrome (TRAPS)
- S56T (p.Ser56Thr), ExAC rs770344578, gnomAD rs770344578, REVEL 0.48, CADD 5.56
- I57L (p.Ile57Leu), TOPMed rs1948087957
- C58F (p.Cys58Phe), rs104895230, ClinGen CA280718, ClinVar RCV000083904, Ensembl rs104895230, REVEL 0.92, AlphaMissense 0.94, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C58G (p.Cys58Gly), rs2136823066, ClinGen CA383550871, ClinVar RCV002017706, Ensembl rs2136823066, AlphaMissense 0.94, MetaLR 0.99, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C58Y (p.Cys58Tyr), rs104895230, ClinGen CA280715, ClinVar RCV000083903, Ensembl rs104895230, AlphaMissense 0.94, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C59F (p.Cys59Phe), rs104895223, ClinGen CA280724, ClinVar RCV000083906, ESP rs104895223, AlphaMissense 0.99, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C59R (p.Cys59Arg), rs104895217, ClinGen CA280149, ClinVar RCV000013130, ClinVar RCV000413303, AlphaMissense 0.99, MetaLR 0.99, Pathogenic, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- C59S (p.Cys59Ser), rs104895223, ClinGen CA280159, ClinVar RCV000013135, ClinVar RCV005411294, REVEL 0.90, AlphaMissense 0.99, Pathogenic/Likely pathogenic, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- C59Y (p.Cys59Tyr), rs104895223, ClinGen CA280721, ClinVar RCV000083905, ClinVar RCV004791264, AlphaMissense 0.99, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- C62G (p.Cys62Gly), rs104895225, ClinGen CA280161, ClinVar RCV000013136, ClinVar RCV000624870, AlphaMissense 0.97, MetaLR 0.99, Likely pathogenic, Inborn genetic diseases
- C62Y (p.Cys62Tyr), rs104895218, ClinGen CA280145, ClinVar RCV000013128, UniProt VAR 013411, AlphaMissense 0.99, MetaLR 1.00, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- G65E (p.Gly65Glu), rs104895239, ClinGen CA280730, ClinVar RCV000083910, Ensembl rs104895239, AlphaMissense 0.99, MetaLR 0.98, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- T66I (p.Thr66Ile), rs104895243, ClinGen CA280733, cosmic curated COSV99369, ClinVar RCV000083911, AlphaMissense 0.93, MetaLR 0.83, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y67C (p.Tyr67Cys), rs104895229, ClinGen CA280739, ClinVar RCV000083913, Ensembl rs104895229, AlphaMissense 0.89, MetaLR 0.80, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y67S (p.Tyr67Ser), rs104895229, ClinGen CA280736, ClinVar RCV000083912, Ensembl rs104895229, AlphaMissense 0.89, MetaLR 0.80, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- L68F (p.Leu68Phe), rs104895262, ClinGen CA280742, ClinVar RCV000083914, Ensembl rs104895262, REVEL 0.57, CADD 20.70, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y69F (p.Tyr69Phe), gnomAD rs1948084832, REVEL 0.31, CADD 12.80
- Y69H (p.Tyr69His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N70S (p.Asn70Ser), rs1948084769, ClinGen CA383550735, cosmic curated COSV50829, ClinVar RCV001303475, AlphaMissense 0.09, MetaLR 0.37, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- D71G (p.Asp71Gly), NCI-TCGA Cosmic COSV5082, cosmic curated COSV50828, Variant assessed as somatic; moderate impact.
- D71V (p.Asp71Val), rs1592047919, ClinGen CA383550726, ClinVar RCV001002432, ClinVar RCV002551695, AlphaMissense 0.76, MetaLR 0.82, Uncertain significance, not specified; TNF receptor-associated periodic fever syndrome (TRAPS)
- C72F (p.Cys72Phe), rs104895252, ClinGen CA383550715, ClinVar RCV002264542, Ensembl rs104895252, REVEL 0.89, AlphaMissense 0.98, Likely pathogenic, Autoinflammatory syndrome
- C72R (p.Cys72Arg), rs104895238, ClinGen CA280748, ClinVar RCV000083916, ClinVar RCV002262668, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Autoinflammatory syndrome
- C72S (p.Cys72Ser), rs104895252, ClinGen CA280754, ClinVar RCV000083918, Ensembl rs104895252, AlphaMissense 0.98, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C72Y (p.Cys72Tyr), rs104895252, ClinGen CA280751, ClinVar RCV000083917, Ensembl rs104895252, AlphaMissense 0.98, MetaLR 1.00, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- P73A (p.Pro73Ala), gnomAD rs1186892329, REVEL 0.24, CADD 11.10
- P73S (p.Pro73Ser), cosmic curated COSV50828, gnomAD rs1186892329, REVEL 0.28, CADD 14.10
- P75L (p.Pro75Leu), rs4149637, ClinGen CA6405585, ClinVar RCV000534430, ClinVar RCV001705299, REVEL 0.38, CADD 22.80, Conflicting interpretations, not specified; not provided; TNF receptor-associated periodic fever syndrome (TR
- P75Q (p.Pro75Gln), 1000Genomes rs4149637, ESP rs4149637, ExAC rs4149637, TOPMed rs4149637, REVEL 0.47, CADD 22.30, Benign, in FPF
- P75R (p.Pro75Arg), 1000Genomes rs4149637, ESP rs4149637, ExAC rs4149637, TOPMed rs4149637, REVEL 0.40, CADD 22.40, Benign, in FPF
- G76E (p.Gly76Glu), TOPMed rs1005736404
- G76V (p.Gly76Val), TOPMed rs1005736404
- D78E (p.Asp78Glu), Ensembl rs1292765870
- T79K (p.Thr79Lys), rs104895219, ClinGen CA280760, ClinVar RCV000083920, Ensembl rs104895219, AlphaMissense 0.61, MetaLR 0.91, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- T79M (p.Thr79Met), rs104895219, ClinGen CA280147, cosmic curated COSV50829, ClinVar RCV000013129, REVEL 0.70, AlphaMissense 0.61, Pathogenic, Multiple sclerosis; not provided; TNF receptor-associated periodic fever syndrom
- D80N (p.Asp80Asn), rs1948084094, ClinGen CA383550640, ClinVar RCV001985654, gnomAD rs1948084094, AlphaMissense 0.30, MetaLR 0.56, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- D80Y (p.Asp80Tyr), gnomAD rs1948084094, REVEL 0.49, AlphaMissense 0.30, Uncertain significance
- C81F (p.Cys81Phe), rs104895220, ClinGen CA280151, ClinVar RCV000013131, ClinVar RCV000286522, REVEL 0.90, CADD 24.80, Pathogenic, not provided
- C81G (p.Cys81Gly), rs104895232, ClinGen CA383550630, ClinVar RCV003513622, AlphaMissense 0.99, MetaLR 1.00, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- C81R (p.Cys81Arg), rs104895232, ClinGen CA280763, ClinVar RCV000083921, Ensembl rs104895232, REVEL 0.89, AlphaMissense 0.99, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C81W (p.Cys81Trp), rs56002980, ClinGen CA280769, ClinVar RCV000083923, TOPMed rs56002980, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- C81Y (p.Cys81Tyr), rs104895220, ClinGen CA280766, ClinVar RCV000083922, Ensembl rs104895220, REVEL 0.90, CADD 24.70, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C84R (p.Cys84Arg), rs104895253, NCI-TCGA TCGA novel, ClinGen CA280775, ClinVar RCV000083925, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Inborn genetic diseases
- C84S (p.Cys84Ser), rs104895224, ClinGen CA280781, ClinVar RCV000083927, Ensembl rs104895224, AlphaMissense 0.99, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C84Y (p.Cys84Tyr), rs104895224, ClinGen CA280778, ClinVar RCV000083926, ClinVar RCV001002161, REVEL 0.91, AlphaMissense 0.99, Pathogenic, not specified; TNF receptor-associated periodic fever syndrome (TRAPS)
- E85D (p.Glu85Asp), rs770439546, ClinGen CA6405583, ClinVar RCV000685835, ExAC rs770439546, REVEL 0.80, CADD 0.25, Likely benign, TNF receptor-associated periodic fever syndrome (TRAPS)
- E85G (p.Glu85Gly), TOPMed rs1948083811
- S86R (p.Ser86Arg), rs201798720, ClinGen CA383550570, ClinVar RCV004473165, ExAC rs201798720, REVEL 0.46, CADD 0.00, Uncertain significance, Inborn genetic diseases
- G87S (p.Gly87Ser), rs1274938366, ClinGen CA383550567, ClinVar RCV003513621, ClinVar RCV005255766, REVEL 0.74, CADD 24.40, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS); not provided
- S88P (p.Ser88Pro), rs104895292, ClinGen CA280784, ClinVar RCV000083928, Ensembl rs104895292, AlphaMissense 0.94, MetaLR 0.48, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- F89I (p.Phe89Ile), rs104895245, ClinGen CA383550552, ClinVar RCV002264543, Ensembl rs104895245, REVEL 0.77, AlphaMissense 0.96, Uncertain significance, Autoinflammatory syndrome
- F89L (p.Phe89Leu), rs104895266, ClinGen CA280796, ClinVar RCV000083932, Ensembl rs104895266, REVEL 0.60, CADD 21.30, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- F89S (p.Phe89Ser), rs104895279, ClinGen CA280793, ClinVar RCV000083931, Ensembl rs104895279, AlphaMissense 0.99, MetaLR 0.84, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- F89V (p.Phe89Val), rs104895245, ClinGen CA280790, ClinVar RCV000083930, Ensembl rs104895245, AlphaMissense 0.96, MetaLR 0.88, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- T90I (p.Thr90Ile), rs34751757, ClinGen CA6405581, ClinVar RCV000756797, ClinVar RCV001078480, REVEL 0.59, AlphaMissense 0.40, Conflicting interpretations, not specified; not provided; TNF receptor-associated periodic fever syndrome (TR
- T90N (p.Thr90Asn), rs34751757, ClinGen CA280797, ClinVar RCV000083933, 1000Genomes rs34751757, AlphaMissense 0.40, MetaLR 0.84, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- T90P (p.Thr90Pro), rs1592047833, ClinGen CA383550542, ClinVar RCV001056333, Ensembl rs1592047833, AlphaMissense 0.84, MetaLR 0.85, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- A91T (p.Ala91Thr), rs1246512040, ClinGen CA383550535, ClinVar RCV001061496, TOPMed rs1246512040, REVEL 0.53, CADD 24.30, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- N94I (p.Asn94Ile), rs104895244, ClinGen CA280800, ClinVar RCV000083934, Ensembl rs104895244, AlphaMissense 0.98, MetaLR 0.89, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- N94K (p.Asn94Lys), rs876661014, ClinGen CA10577455, ClinVar RCV000218061, ClinVar RCV000699281, REVEL 0.69, CADD 24.90, Conflicting interpretations, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- N94T (p.Asn94Thr), Ensembl rs104895244
- N94Y (p.Asn94Tyr), rs1948083279, ClinGen CA383550501, ClinVar RCV001049470, Ensembl rs1948083279, AlphaMissense 0.97, MetaLR 0.89, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- H95L (p.His95Leu), rs104895294, ClinGen CA280806, ClinVar RCV000083936, Ensembl rs104895294, REVEL 0.47, CADD 15.90, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- H95Y (p.His95Tyr), rs104895290, ClinGen CA280803, ClinVar RCV000083935, ClinVar RCV003480056, REVEL 0.53, CADD 3.17, Uncertain significance, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- L96F (p.Leu96Phe), gnomAD rs1369686596
- L96I (p.Leu96Ile), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99369, REVEL 0.31, CADD 12.40, Variant assessed as somatic; moderate impact.
- L96P (p.Leu96Pro), rs104895235, ClinGen CA280809, NCI-TCGA Cosmic COSV9936, cosmic curated COSV99369, REVEL 0.55, CADD 22.40, Uncertain significance, not provided
- H98N (p.His98Asn), ExAC rs755815269, gnomAD rs755815269, REVEL 0.18, CADD 12.40
- C99G (p.Cys99Gly), rs104895228, ClinGen CA280818, ClinVar RCV000083940, Ensembl rs104895228, AlphaMissense 1.00, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C99R (p.Cys99Arg), rs104895228, ClinGen CA280815, ClinVar RCV000083939, ClinVar RCV000214793, AlphaMissense 1.00, MetaLR 1.00, Pathogenic/Likely pathogenic, not provided; TNF receptor-associated periodic fever syndrome (TRAPS)
- C99S (p.Cys99Ser), rs104895228, ClinGen CA280163, ClinVar RCV000013138, UniProt VAR 019304, AlphaMissense 1.00, MetaLR 1.00, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C99Y (p.Cys99Tyr), rs104895231, ClinGen CA280821, ClinVar RCV000083941, Ensembl rs104895231, REVEL 0.88, CADD 26.60, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- S101N (p.Ser101Asn), gnomAD rs1395860016
- C102F (p.Cys102Phe), rs1555108112, ClinGen CA383550413, ClinVar RCV001994995, Ensembl rs1555108112, REVEL 0.94, AlphaMissense 0.99, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C102R (p.Cys102Arg), rs104895236, ClinGen CA280824, ClinVar RCV000083942, Ensembl rs104895236, AlphaMissense 0.99, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C102S (p.Cys102Ser), rs1555108112, ClinGen CA383550414, ClinVar RCV000497456, Ensembl rs1555108112, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, not provided
- C102W (p.Cys102Trp), rs104895249, ClinGen CA280827, ClinVar RCV000083943, Ensembl rs104895249, AlphaMissense 0.99, MetaLR 1.00, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C102Y (p.Cys102Tyr), rs1555108112, ClinGen CA383550416, ClinVar RCV000693373, ClinVar RCV001002362, REVEL 0.95, AlphaMissense 0.99, Pathogenic/Likely pathogenic, not specified; TNF receptor-associated periodic fever syndrome (TRAPS)
- S103C (p.Ser103Cys), rs104895283, ClinGen CA280830, ClinVar RCV000083944, Ensembl rs104895283, AlphaMissense 0.65, MetaLR 0.83, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- C105W (p.Cys105Trp), rs1565468122, ClinGen CA383550379, ClinVar RCV000693612, Ensembl rs1565468122, AlphaMissense 0.99, MetaLR 1.00, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- R106Q (p.Arg106Gln), rs876661031, ClinGen CA10577454, ClinVar RCV000216297, gnomAD rs876661031, REVEL 0.63, CADD 27.80, Likely pathogenic, not provided
- K107N (p.Lys107Asn), rs895885615, ClinGen CA232330292, ClinVar RCV002901947, Ensembl rs895885615, REVEL 0.50, CADD 17.50, Uncertain significance, Inborn genetic diseases
- K107Q (p.Lys107Gln), rs1948082490, ClinGen CA383550370, ClinVar RCV002943798, Ensembl rs1948082490, AlphaMissense 0.12, MetaLR 0.62, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Q111R (p.Gln111Arg), rs2136822038, ClinGen CA383550311, ClinVar RCV001755287, Ensembl rs2136822038, REVEL 0.73, CADD 25.10, Uncertain significance, not provided
- V112M (p.Val112Met), rs201753543, ClinGen CA6405565, ClinVar RCV000756795, ClinVar RCV000823924, REVEL 0.59, CADD 22.40, Uncertain significance, Autoinflammatory syndrome; not specified; not provided
- E113K (p.Glu113Lys), rs2497799391, ClinGen CA383550297, ClinVar RCV003038697, REVEL 0.68, CADD 24.70, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- I114M (p.Ile114Met), cosmic curated COSV10874, Ensembl rs2136822014
- I114S (p.Ile114Ser), gnomAD rs1286690014, REVEL 0.50, CADD 23.80
- S115F (p.Ser115Phe), rs748818440, ClinGen CA6405564, cosmic curated COSV50604, ClinVar RCV002050288, REVEL 0.49, CADD 23.20, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- S115G (p.Ser115Gly), UniProt VAR 019331, Pathogenic, in FPF
- S115P (p.Ser115Pro), rs104895226, ClinGen CA280834, ClinVar RCV000083946, ClinVar RCV002251432, AlphaMissense 0.87, MetaLR 0.80, Uncertain significance, not provided
- C117G (p.Cys117Gly), rs104895221, ClinGen CA383550258, ClinVar RCV002601704, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C117R (p.Cys117Arg), rs104895221, ClinGen CA280153, ClinVar RCV000013132, UniProt VAR 013414, AlphaMissense 0.99, MetaLR 1.00, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- C117Y (p.Cys117Tyr), rs104895222, ClinGen CA280155, ClinVar RCV000013133, UniProt VAR 013415, AlphaMissense 0.99, MetaLR 1.00, Pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- V119A (p.Val119Ala), ExAC rs772756388, gnomAD rs772756388, REVEL 0.41, CADD 14.20
- V119G (p.Val119Gly), ExAC rs772756388, gnomAD rs772756388, REVEL 0.48, CADD 23.60
- D120N (p.Asp120Asn), rs2497799326, ClinGen CA383550231, ClinVar RCV003406052, REVEL 0.39, CADD 15.90, Uncertain significance, TNFRSF1A-related disorder
- R121G (p.Arg121Gly), TOPMed rs104895276, gnomAD rs104895276, REVEL 0.44, CADD 23.30, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- R121P (p.Arg121Pro), rs4149584, ClinGen CA280157, ClinVar RCV000013134, UniProt VAR 019305, REVEL 0.54, CADD 17.90, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- R121Q (p.Arg121Gln), rs4149584, ClinGen CA280920, cosmic curated COSV50610, ClinVar RCV000200263, REVEL 0.56, CADD 2.72, Conflicting interpretations, Autoinflammatory syndrome; not specified; TNF receptor-associated periodic fever
- R121W (p.Arg121Trp), rs104895276, ClinGen CA280837, ClinVar RCV000083947, TOPMed rs104895276, REVEL 0.55, CADD 24.20, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- D122G (p.Asp122Gly), rs2497799280, ClinGen CA383550211, ClinVar RCV003044940, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- T123I (p.Thr123Ile), ExAC rs748101352, gnomAD rs748101352, REVEL 0.92, CADD 26.30
- T123N (p.Thr123Asn), NCI-TCGA Cosmic COSV5059, cosmic curated COSV50599, Variant assessed as somatic; moderate impact.
- V124A (p.Val124Ala), gnomAD rs200801196, REVEL 0.61, CADD 22.00, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- V124G (p.Val124Gly), gnomAD rs200801196, REVEL 0.72, CADD 22.90
- V124M (p.Val124Met), rs104895278, ClinGen CA280843, ClinVar RCV000083949, ClinVar RCV000215355, REVEL 0.69, CADD 23.60, Uncertain significance, Autoinflammatory syndrome; not provided; TNF receptor-associated periodic fever
- C125G (p.Cys125Gly), rs2497799233, ClinGen CA383550183, ClinVar RCV003482050, Uncertain significance, not provided
- C125Y (p.Cys125Tyr), rs104895234, ClinGen CA280846, ClinVar RCV000083950, Ensembl rs104895234, AlphaMissense 0.98, MetaLR 1.00, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- G126D (p.Gly126Asp), gnomAD rs1255943351
- G126S (p.Gly126Ser), Ensembl rs1948078683
- C127Y (p.Cys127Tyr), rs104895242, ClinGen CA280849, ClinVar RCV000083951, Ensembl rs104895242, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, TNF receptor-associated periodic fever syndrome (TRAPS)
- R128G (p.Arg128Gly), rs1592047526, ClinGen CA383550153, ClinVar RCV000804450, ClinVar RCV005231353, REVEL 0.40, CADD 14.20, Uncertain significance, not provided; TNF receptor-associated periodic fever syndrome (TRAPS); not speci
- K129N (p.Lys129Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K129R (p.Lys129Arg), rs1300101062, ClinGen CA383550138, ClinVar RCV002754968, Ensembl rs1300101062, REVEL 0.19, CADD 23.30, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- Q131E (p.Gln131Glu), TOPMed rs1482079303, gnomAD rs1482079303, REVEL 0.73, CADD 25.20
- R133G (p.Arg133Gly), ExAC rs771210186, TOPMed rs771210186, gnomAD rs771210186, REVEL 0.57, CADD 28.40, Likely benign
- R133Q (p.Arg133Gln), rs104895257, ClinGen CA280852, ClinVar RCV000083952, 1000Genomes rs104895257, REVEL 0.57, CADD 13.00, Uncertain significance, TNF receptor-associated periodic fever syndrome (TRAPS)
- R133W (p.Arg133Trp), ExAC rs771210186, TOPMed rs771210186, gnomAD rs771210186, REVEL 0.51, CADD 29.90, Uncertain significance, not provided
- H134N (p.His134Asn), Ensembl rs199618167
- H134P (p.His134Pro), rs104895284, ClinGen CA280855, ClinVar RCV000083953, Ensembl rs104895284, AlphaMissense 0.70, MetaLR 0.47, not provided, TNF receptor-associated periodic fever syndrome (TRAPS)
- Y135C (p.Tyr135Cys), rs2497799077, ClinGen CA383550074, ClinVar RCV003408563, Uncertain significance, TNFRSF1A-related disorder
- Y135H (p.Tyr135His), ExAC rs778922941, gnomAD rs778922941, REVEL 0.35, CADD 9.90
Public TNFRSF1A analysis runs
- TNFRSF1A analysis run — TNFRSF1A (973 variants) — completed 2026-08-19