TREX1 (Three-prime repair exonuclease 1) variants and mutations
TREX1 (also known as Three-prime repair exonuclease 1) is a human protein-coding gene encoding a three-prime repair exonuclease 1 protein. It degrades aberrant cytosolic DNA and prevents inappropriate activation of the cGAS-STING interferon pathway. Pathogenic variants cause interferon-mediated diseases including Aicardi-Goutieres syndrome and familial chilblain lupus, and certain alleles cause retinal vasculopathy with cerebral leukoencephalopathy. This analysis covers 901 TREX1 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes Aicardi-Goutieres syndrome 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio, and systemic lupus erythematosus. Example TREX1 variants include M1T, M1V, and G2A.
Variant analysis overview
- Gene: TREX1
- Protein: Three-prime repair exonuclease 1
- UniProt accession: Q9NSU2
- Organism: Homo sapiens
- Variants analyzed: 901
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 540 unspecified-consequence records; 122 missense variants; 174 synonymous variants; 4 stop-gained variants; 48 frameshift variants; 8 in-frame insertions; 4 in-frame deletions; 2 substitution
- Prediction scores: 675 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Aicardi-Goutieres syndrome 1, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio, systemic lupus erythematosus, chilblain lupus 1, Aicardi-Goutières syndrome, Cerebroretinal vasculopathy, HERNS syndrome, Hereditary vascular retinopathy, Retinal vasculopathy and cerebral leukodystrophy, chilblain lupus, Aicardi-Goutieres syndrome, Intellectual disability.
Protein structure and variant hotspots
- Protein features: 7 binding sites; 3 post-translational modification sites.
- PTM context: 12 variants overlap post-translational modification sites.
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, ClinGen, MaveDB, LitVar.
Notable TREX1 variants
Examples include M1T, M1V, G2A, G2D, G2S, G2V, G2R, G2G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs1179208432, ClinGen CA352616787, ClinVar RCV001962187, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- M1V (p.Met1Val), rs761165865, ClinGen CA2376541, ClinVar RCV001198990, ClinVar RCV001839030, Conflicting interpretations, not provided; Systemic lupus erythematosus; Aicardi-Goutieres syndrome 1
- G2A (p.Gly2Ala), rs2107254550, ClinGen CA2573137190, ClinVar RCV001942306, CADD 17.70, PolyPhen-2 0.06, Pathogenic
- G2D (p.Gly2Asp), 1000Genomes rs199519507, ExAC rs199519507, gnomAD rs199519507, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- G2S (p.Gly2Ser), TOPMed rs2040318477, gnomAD rs2040318477, CADD 22.10
- G2V (p.Gly2Val), rs199519507, ClinGen CA2376542, ClinVar RCV001889344, ClinVar RCV004970408, CADD 23.80, PolyPhen-2 0.76, Uncertain significance, Inborn genetic diseases; Retinal vasculopathy with cerebral leukoencephalopathy
- G2R (p.Gly2Arg), gnomAD 3-48466659-G-C, CADD 23.20, PolyPhen-2 0.86
- G2G (p.Gly2Gly), rs1457063888, gnomAD 3-48466661-C-T, CADD 11.40
- S3L (p.Ser3Leu), rs140029866, ClinGen CA2376543, ClinVar RCV001893160, ClinVar RCV004039177, CADD 22.70, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases; Retinal vasculopathy with cerebral leukoencephalopathy
- S3P (p.Ser3Pro), Ensembl rs2040318925
- S3* (p.Ser3Ter), gnomAD 3-48466663-C-A, CADD 35.00
- S3W (p.Ser3Trp), gnomAD 3-48466663-C-G, CADD 25.00, PolyPhen-2 0.96
- S3S (p.Ser3Ser), rs762687506, gnomAD 3-48466664-G-A, CADD 0.61
- Q4* (p.Gln4Ter), NCI-TCGA Cosmic COSV9960, cosmic curated COSV99604, Variant assessed as somatic; high impact.
- Q4K (p.Gln4Lys), rs2040319464, ClinGen CA352616819, ClinVar RCV002790226, gnomAD rs2040319464, CADD 14.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- A5D (p.Ala5Asp), rs2040319600, ClinGen CA352616838, ClinVar RCV002300171, TOPMed rs2040319600, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- A5V (p.Ala5Val), gnomAD 3-48466669-C-T, CADD 20.50, PolyPhen-2 0.44
- L6L (p.Leu6Leu), rs1560111276, gnomAD 3-48466673-G-C, CADD 0.40
- P7A (p.Pro7Ala), rs2530033254, ClinGen CA2580070045, ClinVar RCV003055644, Pathogenic
- P7R (p.Pro7Arg), rs753028146, ClinGen CA2376547, ClinVar RCV002676321, ExAC rs753028146, CADD 12.00, PolyPhen-2 0.01, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P7S (p.Pro7Ser), rs766068553, ClinGen CA352616858, ClinVar RCV002252648, ExAC rs766068553, CADD 3.22, PolyPhen-2 0.00, Uncertain significance, See cases
- P7T (p.Pro7Thr), ExAC rs766068553, TOPMed rs766068553, gnomAD rs766068553, Uncertain significance
- P7P (p.Pro7Pro), rs761094995, gnomAD 3-48466676-C-T, CADD 3.67
- P8A (p.Pro8Ala), rs754382930, ClinGen CA2376550, ClinVar RCV002650698, ExAC rs754382930, CADD 7.86, PolyPhen-2 0.23, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P8L (p.Pro8Leu), rs561454996, ClinGen CA2376551, ClinVar RCV001367616, ClinVar RCV002547874, CADD 0.28, PolyPhen-2 0.42, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- P8S (p.Pro8Ser), ExAC rs754382930, TOPMed rs754382930, gnomAD rs754382930, Uncertain significance
- P8R (p.Pro8Arg), rs781731683, gnomAD 3-48466673-GC-G, CADD 13.90
- P8P (p.Pro8Pro), rs147463121, gnomAD 3-48466679-G-C, CADD 0.15
- G9E (p.Gly9Glu), rs2040321005, ClinGen CA352616889, ClinVar RCV001314600, Ensembl rs2040321005, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- G9G (p.Gly9Gly), gnomAD 3-48466682-G-A, CADD 1.37
- P10A (p.Pro10Ala), rs781731683, ClinGen CA2376545, ClinVar RCV001225792, ClinVar RCV001291770, Pathogenic
- P10H (p.Pro10His), rs1460993756, ClinGen CA352616896, ClinVar RCV001957617, gnomAD rs1460993756, CADD 13.80, PolyPhen-2 0.06, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P10S (p.Pro10Ser), cosmic curated COSV10733, CADD 15.80, PolyPhen-2 0.12
- P10T (p.Pro10Thr), cosmic curated COSV99604
- P10P (p.Pro10Pro), rs560658691, gnomAD 3-48466685-C-T, CADD 6.82
- M11R (p.Met11Arg), rs1335411387, ClinGen CA352616909, ClinVar RCV000762113, TOPMed rs1335411387, Uncertain significance, not provided
- M11T (p.Met11Thr), rs1335411387, ClinGen CA352616907, ClinVar RCV003037706, TOPMed rs1335411387, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- M11V (p.Met11Val), ExAC rs758675401, TOPMed rs758675401, gnomAD rs758675401
- Q12R (p.Gln12Arg), rs780467272, ClinGen CA2376555, ClinVar RCV001884820, ExAC rs780467272, CADD 23.60, PolyPhen-2 0.01, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- T13P (p.Thr13Pro), gnomAD rs1287600584, CADD 26.20, PolyPhen-2 0.87
- T13S (p.Thr13Ser), gnomAD rs1287600584, CADD 21.50, PolyPhen-2 0.10
- L14F (p.Leu14Phe), rs1560111377, ClinGen CA352616943, ClinVar RCV003001908, Ensembl rs1560111377, CADD 15.80, PolyPhen-2 0.12, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- L14R (p.Leu14Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L14L (p.Leu14Leu), gnomAD 3-48466697-C-T, CADD 12.00
- I15M (p.Ile15Met), rs2530033652, ClinGen CA352616963, ClinVar RCV003129565, Uncertain significance, not provided
- I15V (p.Ile15Val), gnomAD rs1449985027, CADD 17.70, PolyPhen-2 0.01
- p.Ile15dup, rs2040322179, gnomAD 3-48466695-C-CTCA, CADD 20.90
- I15F (p.Ile15Phe), gnomAD 3-48466698-A-T, CADD 26.90
- F17L (p.Phe17Leu), cosmic curated COSV10517
- F17S (p.Phe17Ser), rs531498263, ClinGen CA2376556, ClinVar RCV004531789, ClinVar RCV004587584, CADD 24.90, PolyPhen-2 0.07, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- F17F (p.Phe17Phe), rs1252848366, gnomAD 3-48466706-C-T, CADD 13.40
- D18N (p.Asp18Asn), rs121908117, ClinGen CA116677, ClinVar RCV000004405, ClinVar RCV000114329, Pathogenic, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- D18A (p.Asp18Ala), gnomAD 3-48466708-A-C, CADD 28.60, PolyPhen-2 1.00
- D18D (p.Asp18Asp), gnomAD 3-48466709-C-T, CADD 12.70
- M19L (p.Met19Leu), rs2107255139, ClinGen CA352617007, ClinVar RCV002036152, Ensembl rs2107255139, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- M19N (p.Met19Asn), rs2530033753, ClinGen CA2740094409, ClinVar RCV003800676, Pathogenic
- M19T (p.Met19Thr), rs1560111411, ClinGen CA352617014, ClinVar RCV003791385, Ensembl rs1560111411, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- M19V (p.Met19Val), rs2107255139, ClinGen CA352617009, ClinVar RCV002761239, CADD 19.40, PolyPhen-2 0.01, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- E20G (p.Glu20Gly), rs78300695, gnomAD 3-48466711-T-TG, CADD 28.90
- E20P (p.Glu20Pro), rs770193197, gnomAD 3-48466711-TGGAG-, CADD 32.00
- A21P (p.Ala21Pro), TOPMed rs1356174769, gnomAD rs1356174769, CADD 28.40, PolyPhen-2 0.99, Uncertain significance
- A21T (p.Ala21Thr), rs1356174769, ClinGen CA352617037, ClinVar RCV001928855, TOPMed rs1356174769, CADD 24.70, PolyPhen-2 0.89, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- A21D (p.Ala21Asp), gnomAD 3-48466717-C-A, CADD 26.20, PolyPhen-2 0.99
- A21V (p.Ala21Val), gnomAD 3-48466717-C-T, CADD 27.00, PolyPhen-2 0.99
- T22A (p.Thr22Ala), gnomAD rs1472348056, CADD 26.70, PolyPhen-2 0.99
- T22T (p.Thr22Thr), gnomAD 3-48466721-T-G, CADD 10.20
- G23D (p.Gly23Asp), NCI-TCGA Cosmic COSV5649, NCI-TCGA Cosmic COSV9960, cosmic curated COSV99604, Variant assessed as somatic; moderate impact.
- G23S (p.Gly23Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G23V (p.Gly23Val), cosmic curated COSV56498
- G23C (p.Gly23Cys), gnomAD 3-48466722-G-T, CADD 29.70, PolyPhen-2 1.00
- G23G (p.Gly23Gly), rs1373526164, gnomAD 3-48466724-C-T, CADD 9.08
- L24F (p.Leu24Phe), ExAC rs780921510, CADD 25.60, PolyPhen-2 1.00
- L24L (p.Leu24Leu), rs768580583, gnomAD 3-48466725-T-C, CADD 12.10
- P25A (p.Pro25Ala), rs2530033946, ClinGen CA2740094410, ClinVar RCV003803990, Pathogenic
- P25L (p.Pro25Leu), rs201387759, ClinGen CA2376561, cosmic curated COSV56497, ClinVar RCV003075662, CADD 26.50, PolyPhen-2 0.99, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P25T (p.Pro25Thr), rs748145509, ClinGen CA2376560, ClinVar RCV001239028, ExAC rs748145509, CADD 25.30, PolyPhen-2 0.98, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- P25S (p.Pro25Ser), gnomAD 3-48466728-C-T, CADD 25.80, PolyPhen-2 0.96
- P25P (p.Pro25Pro), gnomAD 3-48466730-C-G, CADD 11.60
- F26L (p.Phe26Leu), ExAC rs772753856, gnomAD rs772753856, CADD 20.20, PolyPhen-2 0.23
- F26S (p.Phe26Ser), cosmic curated COSV10517, CADD 16.80, PolyPhen-2 0.01
- F26V (p.Phe26Val), ExAC rs772753856, gnomAD rs772753856, CADD 21.50, PolyPhen-2 0.37
- F26F (p.Phe26Phe), rs770565869, gnomAD 3-48466733-C-T, CADD 13.40
- S27P (p.Ser27Pro), Ensembl rs2107255373, CADD 27.10, PolyPhen-2 0.77
- S27F (p.Ser27Phe), rs11548268, ClinGen CA2376565, ClinVar RCV001926564, ClinVar RCV004529053, CADD 27.10, PolyPhen-2 0.94, Uncertain significance, TREX1-related disorder; Retinal vasculopathy with cerebral leukoencephalopathy a
- S27S (p.Ser27Ser), rs1308074815, gnomAD 3-48466736-C-G, CADD 11.20
- Q28H (p.Gln28His), rs867996558, ClinGen CA352617133, ClinVar RCV003437826, ClinVar RCV003778426, Uncertain significance, not provided; Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral l
- Q28R (p.Gln28Arg), rs1369567808, ClinGen CA352617128, cosmic curated COSV10517, ClinVar RCV001967181, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P29S (p.Pro29Ser), rs1407557314, ClinGen CA352617142, NCI-TCGA Cosmic COSV5649, cosmic curated COSV56496, CADD 25.90, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- K30E (p.Lys30Glu), rs760972495, ClinGen CA2376566, cosmic curated COSV10517, ClinVar RCV002671534, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- K30N (p.Lys30Asn), gnomAD rs1243784456, CADD 25.20, PolyPhen-2 0.86
- K30R (p.Lys30Arg), gnomAD rs1340882700, CADD 22.70, PolyPhen-2 0.37
- K30* (p.Lys30Ter), gnomAD 3-48466743-A-T, CADD 37.00
- V31I (p.Val31Ile), rs1057321761, ClinGen CA73932472, ClinVar RCV002023436, TOPMed rs1057321761, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- T32M (p.Thr32Met), rs755138065, ClinGen CA2376567, ClinVar RCV001317878, ClinVar RCV001824950, CADD 26.10, PolyPhen-2 1.00, Uncertain significance, not provided; not specified; Aicardi-Goutieres syndrome 1
- T32R (p.Thr32Arg), ExAC rs755138065, TOPMed rs755138065, gnomAD rs755138065, CADD 26.40, PolyPhen-2 1.00, Uncertain significance
- T32T (p.Thr32Thr), rs754260689, gnomAD 3-48466751-G-A, CADD 7.54
- E33V (p.Glu33Val), rs2530034374, ClinGen CA352617195, ClinVar RCV002302113, CADD 28.60, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- E33K (p.Glu33Lys), gnomAD 3-48466752-G-A, CADD 29.80, PolyPhen-2 1.00
- L34L (p.Leu34Leu), rs1295070952, gnomAD 3-48466755-C-T, CADD 13.30
- C35A (p.Cys35Ala), rs778172075, gnomAD 3-48466757-GT-G, CADD 30.00
- L37L (p.Leu37Leu), rs762407345, gnomAD 3-48466764-C-T, CADD 13.10
- A38S (p.Ala38Ser), rs765715997, ClinGen CA2376571, ClinVar RCV002021281, ExAC rs765715997, CADD 29.70, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- A38V (p.Ala38Val), rs2040326850, ClinGen CA352617254, ClinVar RCV002029169, TOPMed rs2040326850, CADD 26.90, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- V39L (p.Val39Leu), ESP rs145434330, ExAC rs145434330, TOPMed rs145434330, gnomAD rs145434330, CADD 15.80, PolyPhen-2 0.11, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- V39V (p.Val39Val), rs2040327217, gnomAD 3-48466772-C-G, CADD 14.50
- H40Y (p.His40Tyr), gnomAD 3-48466773-C-T, CADD 24.70, PolyPhen-2 0.96
- H40H (p.His40His), rs758622317, gnomAD 3-48466775-C-T, CADD 14.70
- H40Q (p.His40Gln), gnomAD 3-48466775-C-G, CADD 28.70, PolyPhen-2 0.93
- C42R (p.Cys42Arg), cosmic curated COSV10517
- C42W (p.Cys42Trp), rs2530034686, ClinGen CA352617307, ClinVar RCV003056980, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- C42Y (p.Cys42Tyr), rs2107255814, ClinGen CA352617304, ClinVar RCV002248271, Ensembl rs2107255814, CADD 16.60, PolyPhen-2 0.00, Uncertain significance, not provided
- A43S (p.Ala43Ser), rs780414238, ClinGen CA352617314, ClinVar RCV001068389, ExAC rs780414238, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- A43T (p.Ala43Thr), rs780414238, ClinGen CA2376574, ClinVar RCV002020058, ExAC rs780414238, CADD 25.50, PolyPhen-2 0.60, Uncertain significance, Inborn genetic diseases; Aicardi-Goutieres syndrome 1; Chilblain lupus 1
- L44P (p.Leu44Pro), cosmic curated COSV56497
- L44Q (p.Leu44Gln), rs2530034789, ClinGen CA352617326, ClinVar RCV004473547, Uncertain significance, Inborn genetic diseases
- L44L (p.Leu44Leu), rs2107255846, gnomAD 3-48466787-G-C, CADD 11.60
- E45R (p.Glu45Arg), cosmic curated COSV10453
- S46N (p.Ser46Asn), cosmic curated COSV10517, Ensembl rs1315445082
- S46R (p.Ser46Arg), rs2107255865, ClinGen CA2499216809, ClinVar RCV001730099, ClinVar RCV002286847, CADD 13.40, PolyPhen-2 0.00, Pathogenic
- S46T (p.Ser46Thr), gnomAD 3-48466792-G-C, CADD 10.80, PolyPhen-2 0.01
- S46S (p.Ser46Ser), rs895463771, gnomAD 3-48466793-C-T, CADD 8.74
- P47A (p.Pro47Ala), ExAC rs751831423, gnomAD rs751831423, CADD 1.04, PolyPhen-2 0.00, Uncertain significance
- P47H (p.Pro47His), rs1012563521, ClinGen CA73932530, ClinVar RCV003798866, TOPMed rs1012563521, CADD 17.60, PolyPhen-2 0.54, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P47S (p.Pro47Ser), rs751831423, ClinGen CA352617365, ClinVar RCV003786135, ExAC rs751831423, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P47T (p.Pro47Thr), rs751831423, ClinGen CA352617362, cosmic curated COSV10517, ClinVar RCV001956710, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P47P (p.Pro47Pro), gnomAD 3-48466796-C-T, CADD 3.15
- P48L (p.Pro48Leu), rs2040328677, ClinGen CA352617379, ClinVar RCV001309567, Ensembl rs2040328677, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P48R (p.Pro48Arg), rs2040328677, ClinGen CA352617380, ClinVar RCV003798939, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P48S (p.Pro48Ser), rs754776272, cosmic curated COSV10517, ClinGen CA2376577, cosmic curated COSV99604, CADD 1.93, PolyPhen-2 0.01, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P48A (p.Pro48Ala), gnomAD 3-48466797-C-G, CADD 1.85, PolyPhen-2 0.01
- P48H (p.Pro48His), gnomAD 3-48466798-C-A, CADD 20.40, PolyPhen-2 0.80
- P48P (p.Pro48Pro), rs781060789, gnomAD 3-48466799-C-G, CADD 3.15
- T49A (p.Thr49Ala), rs1427260162, ClinGen CA352617387, ClinVar RCV001722444, gnomAD rs1427260162, CADD 2.23, PolyPhen-2 0.00, Likely benign, not provided
- T49I (p.Thr49Ile), cosmic curated COSV10517
- T49H (p.Thr49His), rs748914604, gnomAD 3-48466792-G-GC, CADD 23.00
- T49P (p.Thr49Pro), rs748914604, gnomAD 3-48466792-GC-G, CADD 21.50
- T49T (p.Thr49Thr), rs756046037, gnomAD 3-48466802-C-T, CADD 1.78
- S50F (p.Ser50Phe), cosmic curated COSV99062, Ensembl rs1560111684, CADD 16.60, PolyPhen-2 0.47, Uncertain significance, not specified
- Q51* (p.Gln51Ter), cosmic curated COSV56498
- Q51P (p.Gln51Pro), rs2107256110, ClinGen CA352617415, ClinVar RCV001966962, Ensembl rs2107256110, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- Q51R (p.Gln51Arg), rs773808155, ClinGen CA2376582, ClinVar RCV000318517, ClinVar RCV005025421, CADD 8.85, PolyPhen-2 0.01, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- Q51G (p.Gln51Gly), rs770607110, gnomAD 3-48466801-CCT-C, CADD 17.60
- Q51Q (p.Gln51Gln), rs1331908804, gnomAD 3-48466808-G-A, CADD 1.81
- G52W (p.Gly52Trp), gnomAD rs1328154001, CADD 22.60, PolyPhen-2 0.99
- P53H (p.Pro53His), cosmic curated COSV10517
- P53T (p.Pro53Thr), ExAC rs777638105, gnomAD rs777638105, CADD 7.07, PolyPhen-2 0.11
- P53S (p.Pro53Ser), gnomAD 3-48466812-C-T, CADD 6.59, PolyPhen-2 0.06
- P53P (p.Pro53Pro), gnomAD 3-48466814-A-G, CADD 1.10
- P54H (p.Pro54His), cosmic curated COSV56496
- P54R (p.Pro54Arg), Ensembl rs1315987398, CADD 6.12, PolyPhen-2 0.01
- P54S (p.Pro54Ser), Ensembl rs2040329904
- P54L (p.Pro54Leu), gnomAD 3-48466816-C-T, CADD 7.44, PolyPhen-2 0.00
- P55L (p.Pro55Leu), rs2530035319, ClinGen CA352617469, ClinVar RCV004473548, ClinVar RCV005220900, CADD 9.49, PolyPhen-2 0.02, Uncertain significance, Inborn genetic diseases; Chilblain lupus 1; Aicardi-Goutieres syndrome 1
- P55S (p.Pro55Ser), ESP rs148664129, ExAC rs148664129, gnomAD rs148664129, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P55P (p.Pro55Pro), gnomAD 3-48466820-C-T, CADD 3.76
- T56A (p.Thr56Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T56P (p.Thr56Pro), TOPMed rs2040330463, CADD 4.97, PolyPhen-2 0.00
- T56S (p.Thr56Ser), rs759104641, gnomAD 3-48466819-CCA-C, CADD 16.60
- T56T (p.Thr56Thr), rs770441459, gnomAD 3-48466823-A-T, CADD 0.27
- P58L (p.Pro58Leu), rs745552589, ClinGen CA2376588, ClinVar RCV003076316, ExAC rs745552589, CADD 23.60, PolyPhen-2 1.00, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P58S (p.Pro58Ser), rs773927064, ClinGen CA2376587, ClinVar RCV002729093, ClinVar RCV005227828, CADD 23.20, PolyPhen-2 1.00, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P58H (p.Pro58His), rs1156394177, gnomAD 3-48466826-TCCTC-, CADD 23.80
- P58A (p.Pro58Ala), gnomAD 3-48466827-C-G, CADD 21.00, PolyPhen-2 0.99
- P59S (p.Pro59Ser), TOPMed rs1200269206, gnomAD rs1200269206, CADD 2.83, PolyPhen-2 0.01, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P59P (p.Pro59Pro), rs2040331259, gnomAD 3-48466832-A-G, CADD 0.67
- P60S (p.Pro60Ser), rs768962835, ClinGen CA2376589, ClinVar RCV003801901, ClinVar RCV004818417, CADD 13.80, PolyPhen-2 0.10, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- P61L (p.Pro61Leu), rs777034646, ClinGen CA2376590, ClinVar RCV001944472, ExAC rs777034646, CADD 23.80, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P61Q (p.Pro61Gln), rs777034646, ClinGen CA73932620, ClinVar RCV000987264, ClinVar RCV001759678, CADD 23.60, PolyPhen-2 1.00, Conflicting interpretations, not provided; Aicardi-Goutieres syndrome 1; See cases
- P61R (p.Pro61Arg), rs777034646, ClinGen CA352617537, ClinVar RCV002028121, ExAC rs777034646, CADD 23.70, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- P61S (p.Pro61Ser), gnomAD rs1449073652, CADD 23.40, PolyPhen-2 1.00
- P61P (p.Pro61Pro), rs55852466, gnomAD 3-48466838-G-A, CADD 1.95
- R62C (p.Arg62Cys), rs532286717, ClinGen CA2376592, ClinVar RCV001069845, ClinVar RCV002554590, CADD 26.00, PolyPhen-2 1.00, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- R62G (p.Arg62Gly), rs532286717, ClinGen CA352617541, ClinVar RCV002300219, 1000Genomes rs532286717, CADD 24.90, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- R62H (p.Arg62His), rs547752029, ClinGen CA2376594, ClinVar RCV001864038, ClinVar RCV004690150, CADD 25.90, PolyPhen-2 1.00, Uncertain significance, not specified; Retinal vasculopathy with cerebral leukoencephalopathy and system
- R62L (p.Arg62Leu), rs547752029, ClinGen CA352617551, ClinVar RCV002046314, 1000Genomes rs547752029, CADD 25.70, PolyPhen-2 1.00, Uncertain significance, Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestatio
- R62P (p.Arg62Pro), 1000Genomes rs547752029, ExAC rs547752029, TOPMed rs547752029, gnomAD rs547752029, CADD 26.10, PolyPhen-2 1.00, Uncertain significance
- V63M (p.Val63Met), rs2040332362, ClinGen CA352617553, ClinVar RCV003065161, TOPMed rs2040332362, CADD 24.50, PolyPhen-2 1.00, Uncertain significance, Aicardi-Goutieres syndrome 1; Chilblain lupus 1; Retinal vasculopathy with cereb
- V64A (p.Val64Ala), rs763056226, ClinGen CA2376595, ClinVar RCV001048363, ExAC rs763056226, CADD 17.40, PolyPhen-2 0.06, Uncertain significance, Aicardi-Goutieres syndrome 1; Retinal vasculopathy with cerebral leukoencephalop
- V64L (p.Val64Leu), gnomAD 3-48466845-G-T, CADD 13.10, PolyPhen-2 0.00
- V64I (p.Val64Ile), gnomAD 3-48466845-G-A, CADD 14.00, PolyPhen-2 0.04
Public TREX1 analysis runs
- TREX1 analysis run — TREX1 (901 variants) — completed 2026-08-22