NRXN1 (Neurexin-1) variants and mutations
NRXN1 (also known as Neurexin-1) is a human protein-coding gene encoding a neurexin-1 protein. It helps organize presynaptic adhesion and aligns neurotransmitter-release machinery with postsynaptic partners through interactions with neuroligins and other ligands. Haploinsufficiency and disruptive variants increase risk for neurodevelopmental disorders including intellectual disability, autism, epilepsy, and schizophrenia. This analysis covers 3,001 NRXN1 variants and mutations. Of these, 59% have computational variant effect predictions. Disease context includes Pitt-Hopkins-like syndrome 2, hereditary disease, and autism spectrum disorder. Example NRXN1 variants include M1?, M1I, and M1K.
Variant analysis overview
- Gene: NRXN1
- Protein: Neurexin-1
- UniProt accession: Q9ULB1
- Organism: Homo sapiens
- Variants analyzed: 3001
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,738 unspecified-consequence records; 71 synonymous variants; 4 stop-gained variants; 173 missense variants; 9 frameshift variants; 2 in-frame deletions; 2 splice-region variants; 1 stop lost; 1 substitution
- Prediction scores: 1,782 variants have prediction scores (59% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Pitt-Hopkins-like syndrome 2, hereditary disease, autism spectrum disorder, Abnormality of the skeletal system, chromosome 2p16.3 deletion syndrome, complex neurodevelopmental disorder, autism, Intellectual disability, major depressive disorder, Pitt-Hopkins-like syndrome, Pitt-Hopkins or Pitt-Hopkins-like syndrome, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 9 domains; 10 binding sites; 5 post-translational modification sites.
- Structural context: 2,355 variants have structural context.
- PTM context: 10 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, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable NRXN1 variants
Examples include M1?, M1I, M1K, M1T, G2E, G2R, G2W, T3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV68050
- M1I (p.Met1Ile), rs1678450230, gnomAD 2-49973992-C-A, CADD 18.70, SIFT 0.34
- M1K (p.Met1Lys), gnomAD 2-49973993-A-T, CADD 20.00, SIFT 0.07
- M1T (p.Met1Thr), rs1573151656, gnomAD 2-49973993-A-G, CADD 20.40, SIFT 0.10
- G2E (p.Gly2Glu), cosmic curated COSV10533, Ensembl rs947102418, REVEL 0.21, CADD 22.80
- G2R (p.Gly2Arg), rs867477898, ClinGen CA346824900, ClinVar RCV003818950, TOPMed rs867477898, REVEL 0.22, CADD 23.30, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G2W (p.Gly2Trp), cosmic curated COSV68003, TOPMed rs867477898, gnomAD rs867477898, REVEL 0.22, CADD 26.00, Uncertain significance
- T3K (p.Thr3Lys), rs1670941293, ClinGen CA346824894, ClinVar RCV001932146, Ensembl rs1670941293, REVEL 0.15, CADD 23.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- T3M (p.Thr3Met), rs1670941293, ClinGen CA346824892, cosmic curated COSV68023, ClinVar RCV001320024, REVEL 0.17, CADD 23.10, Uncertain significance, Pitt-Hopkins-like syndrome 2
- A4E (p.Ala4Glu), gnomAD rs1198368082, REVEL 0.21, CADD 20.20, Uncertain significance
- A4G (p.Ala4Gly), gnomAD rs1198368082, REVEL 0.18, CADD 20.40, Uncertain significance
- A4T (p.Ala4Thr), rs201209686, ClinGen CA48054952, cosmic curated COSV68037, ClinVar RCV002616047, REVEL 0.17, CADD 21.40, Uncertain significance, Pitt-Hopkins-like syndrome 2
- A4V (p.Ala4Val), rs1198368082, ClinGen CA346824887, ClinVar RCV000814987, gnomAD rs1198368082, REVEL 0.08, CADD 18.30, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L5P (p.Leu5Pro), rs2105335336, ClinGen CA346824883, ClinVar RCV001752979, ClinVar RCV002540674, REVEL 0.25, CADD 23.20, Uncertain significance, Pitt-Hopkins-like syndrome 2; not provided
- L6F (p.Leu6Phe), gnomAD rs1416531341, CADD 20.40
- L6H (p.Leu6His), rs1220439982, ClinGen CA346824877, ClinVar RCV002839436, TOPMed rs1220439982, CADD 20.90, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L6P (p.Leu6Pro), rs1220439982, ClinGen CA346824876, ClinVar RCV003509261, TOPMed rs1220439982, CADD 21.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L6V (p.Leu6Val), gnomAD rs1416531341, CADD 20.10
- Q7* (p.Gln7Ter), Ensembl rs2105335266, CADD 37.00
- Q7H (p.Gln7His), TOPMed rs888358406, REVEL 0.17, CADD 21.30
- Q7L (p.Gln7Leu), rs1558617775, ClinGen CA346824870, ClinVar RCV000706465, Ensembl rs1558617775, REVEL 0.26, CADD 21.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- Q7R (p.Gln7Arg), rs1558617775, ClinGen CA346824871, ClinVar RCV002317606, Ensembl rs1558617775, REVEL 0.13, CADD 18.50, Uncertain significance, Inborn genetic diseases
- R8C (p.Arg8Cys), NCI-TCGA TCGA novel, REVEL 0.20, CADD 24.50, Variant assessed as somatic; moderate impact.
- R8G (p.Arg8Gly), TOPMed rs1054998116
- R8H (p.Arg8His), cosmic curated COSV68030, REVEL 0.15, CADD 23.10, Uncertain significance, Pitt-Hopkins-like syndrome 2
- R8L (p.Arg8Leu), rs796052765, ClinGen CA316081, ClinVar RCV000188245, TOPMed rs796052765, REVEL 0.21, CADD 23.00, Uncertain significance, not provided
- R8R (p.Arg8Arg), rs1284126790, gnomAD 2-49973989-T-C, CADD 20.50
- G9E (p.Gly9Glu), rs1670933863, ClinGen CA346824861, ClinVar RCV002914865, TOPMed rs1670933863, REVEL 0.26, CADD 21.90, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G9R (p.Gly9Arg), rs1443893312, TOPMed rs1443893312, ClinGen CA346824863, ClinVar RCV001904474, CADD 17.70, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G10C (p.Gly10Cys), rs777530225, ClinGen CA346824857, ClinVar RCV000997144, ExAC rs777530225, REVEL 0.55, CADD 25.60, Uncertain significance, not provided
- G10D (p.Gly10Asp), ExAC rs757927343, TOPMed rs757927343, gnomAD rs757927343, REVEL 0.50, CADD 24.50, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G10S (p.Gly10Ser), rs777530225, ClinGen CA1655570, cosmic curated COSV68051, ClinVar RCV000519914, REVEL 0.47, CADD 22.50, Uncertain significance, not provided; Pitt-Hopkins-like syndrome 2
- G10V (p.Gly10Val), ExAC rs757927343, TOPMed rs757927343, gnomAD rs757927343, REVEL 0.38, CADD 22.90
- C11R (p.Cys11Arg), Ensembl rs1575279892, REVEL 0.51, CADD 23.40
- C11Y (p.Cys11Tyr), rs796052766, ClinGen CA316083, ClinVar RCV000188246, ClinVar RCV001315923, REVEL 0.52, CADD 23.10, Uncertain significance, Inborn genetic diseases; not provided; Pitt-Hopkins-like syndrome 2
- C11S (p.Cys11Ser), gnomAD 2-49973981-C-G, CADD 19.00, SIFT 0.01
- C11G (p.Cys11Gly), rs1201505710, gnomAD 2-49973982-A-C, CADD 20.30, SIFT 0.01
- F12C (p.Phe12Cys), rs1298445857, ClinGen CA346824842, ClinVar RCV000698366, ClinVar RCV002315998, REVEL 0.18, CADD 17.30, Uncertain significance, Inborn genetic diseases; Pitt-Hopkins-like syndrome 2
- F12L (p.Phe12Leu), TOPMed rs1374501973, gnomAD rs1374501973, CADD 4.55, Likely benign
- L13F (p.Leu13Phe), rs201674835, ClinGen CA1655568, cosmic curated COSV10470, ClinVar RCV001219129, REVEL 0.35, CADD 17.70, Conflicting interpretations, not provided; Pitt-Hopkins-like syndrome 2; Inborn genetic diseases
- L13P (p.Leu13Pro), cosmic curated COSV10892, REVEL 0.51, CADD 23.60
- L13S (p.Leu13Ser), rs9636391, gnomAD 2-49973972-A-G, CADD 20.40, SIFT 0.65
- L14M (p.Leu14Met), rs1670928980, ClinGen CA346824834, ClinVar RCV001062694, Ensembl rs1670928980, REVEL 0.23, CADD 19.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L14P (p.Leu14Pro), TOPMed rs1307554186, REVEL 0.53, CADD 23.90, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L14R (p.Leu14Arg), TOPMed rs1307554186
- C15* (p.Cys15Ter), NCI-TCGA Cosmic COSV6803, cosmic curated COSV68031, CADD 36.00, Variant assessed as somatic; high impact.
- C15Y (p.Cys15Tyr), rs1670927864, ClinGen CA346824826, ClinVar RCV003511200, TOPMed rs1670927864, REVEL 0.34, CADD 17.90, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L16F (p.Leu16Phe), NCI-TCGA TCGA novel, REVEL 0.45, CADD 22.10, Variant assessed as somatic; moderate impact.
- S17* (p.Ser17Ter), gnomAD rs868375208, CADD 37.00
- S17L (p.Ser17Leu), rs868375208, NCI-TCGA Cosmic COSV6801, cosmic curated COSV68016, gnomAD rs868375208, REVEL 0.35, CADD 21.60, Variant assessed as somatic; moderate impact.
- L18M (p.Leu18Met), Ensembl rs199975231, REVEL 0.52, CADD 23.50
- L18Q (p.Leu18Gln), Ensembl rs56173198, REVEL 0.47, CADD 23.80, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L20P (p.Leu20Pro), gnomAD rs1670923027, REVEL 0.60, CADD 24.60, Uncertain significance
- L20R (p.Leu20Arg), rs1670923027, ClinGen CA346824797, ClinVar RCV001067477, gnomAD rs1670923027, REVEL 0.58, CADD 26.10, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L21P (p.Leu21Pro), Ensembl rs1670922082, REVEL 0.62, CADD 27.40
- G22C (p.Gly22Cys), cosmic curated COSV68001, CADD 14.90
- G22D (p.Gly22Asp), rs1575279682, ClinGen CA346824788, ClinVar RCV000818406, Ensembl rs1575279682, CADD 16.50, Uncertain significance, Pitt-Hopkins-like syndrome 2
- C23S (p.Cys23Ser), Ensembl rs1670921246
- C23Y (p.Cys23Tyr), Ensembl rs1670921246, REVEL 0.61, CADD 23.70
- W24* (p.Trp24Ter), gnomAD rs1477139182, CADD 37.00
- W24C (p.Trp24Cys), gnomAD rs1477139182, REVEL 0.39, CADD 22.80
- W24R (p.Trp24Arg), NCI-TCGA TCGA novel, REVEL 0.42, CADD 23.00, Variant assessed as somatic; moderate impact.
- W24S (p.Trp24Ser), gnomAD rs1670920288, REVEL 0.33, CADD 22.80
- A25E (p.Ala25Glu), cosmic curated COSV68048, REVEL 0.49, CADD 25.30
- A25S (p.Ala25Ser), cosmic curated COSV68012, REVEL 0.30, CADD 21.20
- A25T (p.Ala25Thr), gnomAD rs1670919200, REVEL 0.40, CADD 22.20
- A25V (p.Ala25Val), NCI-TCGA Cosmic COSV6804, REVEL 0.25, CADD 18.80, Variant assessed as somatic; moderate impact.
- E26* (p.Glu26Ter), ExAC rs201847846, TOPMed rs201847846, gnomAD rs201847846, CADD 37.00, Uncertain significance
- E26D (p.Glu26Asp), TOPMed rs1472878753, gnomAD rs1472878753, REVEL 0.14, CADD 16.50
- E26K (p.Glu26Lys), rs201847846, ClinGen CA346824761, ClinVar RCV000824207, ExAC rs201847846, REVEL 0.41, CADD 20.40, Uncertain significance, Pitt-Hopkins-like syndrome 2
- E26Q (p.Glu26Gln), rs201847846, ClinGen CA1655564, ClinVar RCV000498110, ClinVar RCV001225086, REVEL 0.40, CADD 20.60, Uncertain significance, Pitt-Hopkins-like syndrome 2; Inborn genetic diseases; not provided
- E26E (p.Glu26Glu), gnomAD 2-49973977-T-C, CADD 19.40
- E26A (p.Glu26Ala), rs1345161055, gnomAD 2-49973978-T-G, CADD 20.10, SIFT 0.23
- L27M (p.Leu27Met), cosmic curated COSV68052, REVEL 0.21, CADD 20.40, Uncertain significance, Pitt-Hopkins-like syndrome 2
- L27V (p.Leu27Val), gnomAD rs1670916214, REVEL 0.20, CADD 18.10, Likely benign
- G28A (p.Gly28Ala), rs199598542, ClinGen CA1655563, ClinVar RCV001319832, UniProt VAR 070274, CADD 19.70, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G28C (p.Gly28Cys), rs200709052, ClinGen CA48054944, ClinVar RCV002294782, Ensembl rs200709052, REVEL 0.47, CADD 24.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- S29I (p.Ser29Ile), cosmic curated COSV10972, ESP rs373013874, TOPMed rs373013874, gnomAD rs373013874, REVEL 0.32, CADD 18.70
- S29R (p.Ser29Arg), rs1670913788, ClinGen CA346824746, ClinVar RCV003621243, Ensembl rs1670913788, REVEL 0.41, CADD 20.60, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G30E (p.Gly30Glu), cosmic curated COSV10470, REVEL 0.66, CADD 25.30
- G30R (p.Gly30Arg), rs752126111, ClinGen CA1655562, ClinVar RCV003621131, ExAC rs752126111, REVEL 0.55, CADD 25.70, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G30W (p.Gly30Trp), ExAC rs752126111, TOPMed rs752126111, gnomAD rs752126111, REVEL 0.56, CADD 26.70, Uncertain significance
- L31M (p.Leu31Met), NCI-TCGA TCGA novel, CADD 19.30, Variant assessed as somatic; moderate impact.
- E32* (p.Glu32Ter), cosmic curated COSV68013, CADD 37.00
- F33L (p.Phe33Leu), rs2105334367, ClinGen CA346824715, ClinVar RCV001776860, Ensembl rs2105334367, REVEL 0.82, CADD 25.00, Uncertain significance, not provided
- F33V (p.Phe33Val), cosmic curated COSV10593
- P34L (p.Pro34Leu), NCI-TCGA TCGA novel, REVEL 0.38, CADD 22.50, Variant assessed as somatic; moderate impact.
- P34S (p.Pro34Ser), cosmic curated COSV10824, TOPMed rs1228817558, gnomAD rs1228817558, REVEL 0.25, CADD 19.70
- G35S (p.Gly35Ser), TOPMed rs1460174762, gnomAD rs1460174762, REVEL 0.76, CADD 26.20
- A36T (p.Ala36Thr), cosmic curated COSV99065, Ensembl rs2105334289, REVEL 0.17, CADD 16.10
- E37K (p.Glu37Lys), cosmic curated COSV68055, REVEL 0.39, CADD 22.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- E37Q (p.Glu37Gln), rs910774989, ClinGen CA48054941, ClinVar RCV001757397, gnomAD rs910774989, REVEL 0.36, CADD 20.50, Uncertain significance, not provided
- G38D (p.Gly38Asp), rs1553517468, ClinGen CA346824686, ClinVar RCV000649739, Ensembl rs1553517468, REVEL 0.55, CADD 25.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G38N (p.Gly38Asn), cosmic curated COSV68029
- G38S (p.Gly38Ser), rs759779535, ClinGen CA1655558, ClinVar RCV003032170, ExAC rs759779535, REVEL 0.25, CADD 22.40, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G38G (p.Gly38Gly), rs983505229, gnomAD 2-49926389-C-T, CADD 0.33
- G38A (p.Gly38Ala), rs558526081, gnomAD 2-49926390-C-G, CADD 1.88, SIFT 0.09
- G38V (p.Gly38Val), gnomAD 2-49926390-C-A, CADD 3.10, SIFT 0.01
- G38E (p.Gly38Glu), rs558526081, gnomAD 2-49926390-C-T, CADD 3.14, SIFT 0.06
- Q39Q (p.Gln39Gln), rs750495130, gnomAD 2-49926380-C-T, CADD 0.33
- W40* (p.Trp40Ter), rs1064795493, ClinGen CA16617739, ClinVar RCV000484849, Ensembl rs1064795493, CADD 38.00, Likely pathogenic
- T41M (p.Thr41Met), rs995509296, ClinGen CA48054940, NCI-TCGA Cosmic COSV6800, cosmic curated COSV68003, REVEL 0.44, CADD 26.60, Uncertain significance, Pitt-Hopkins-like syndrome 2; Inborn genetic diseases
- T41T (p.Thr41Thr), rs992567781, gnomAD 2-49926365-A-C, CADD 3.62
- T41N (p.Thr41Asn), rs950845853, gnomAD 2-49926378-G-T, CADD 0.57, SIFT 0.02
- T41K (p.Thr41Lys), rs1431696206, gnomAD 2-49926387-G-T, CADD 3.41, SIFT 0.18
- R42C (p.Arg42Cys), cosmic curated COSV68004, TOPMed rs1365577683, gnomAD rs1365577683, REVEL 0.70, CADD 29.60
- R42G (p.Arg42Gly), TOPMed rs1365577683, gnomAD rs1365577683, REVEL 0.68, CADD 26.90
- R42H (p.Arg42His), rs1166363453, NCI-TCGA Cosmic COSV6801, cosmic curated COSV68014, gnomAD rs1166363453, REVEL 0.74, CADD 25.20, Variant assessed as somatic; moderate impact.
- R42R (p.Arg42Arg), gnomAD 2-49926359-T-C, CADD 6.06
- R42T (p.Arg42Thr), gnomAD 2-49926360-C-G, CADD 1.56
- F43L (p.Phe43Leu), rs1216338017, ClinGen CA346824656, ClinVar RCV002385384, TOPMed rs1216338017, REVEL 0.60, CADD 22.40, Uncertain significance, Inborn genetic diseases
- F43S (p.Phe43Ser), rs2105334074, ClinGen CA346824653, ClinVar RCV002006334, Ensembl rs2105334074, REVEL 0.84, CADD 28.50, Uncertain significance, Pitt-Hopkins-like syndrome 2
- P44L (p.Pro44Leu), rs1670900195, ClinGen CA346824643, ClinVar RCV001306821, Ensembl rs1670900195, REVEL 0.24, CADD 21.70, Uncertain significance, Pitt-Hopkins-like syndrome 2
- P44S (p.Pro44Ser), cosmic curated COSV10470, REVEL 0.18, CADD 20.70
- P44Q (p.Pro44Gln), gnomAD 2-49926342-G-T, CADD 0.55
- K45Q (p.Lys45Gln), gnomAD rs1472275567, REVEL 0.34, CADD 22.60
- K45R (p.Lys45Arg), rs1670899012, ClinGen CA346824638, ClinVar RCV002301600, gnomAD rs1670899012, REVEL 0.23, CADD 20.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- K45E (p.Lys45Glu), gnomAD 2-49926370-T-C, CADD 5.45
- W46* (p.Trp46Ter), rs1238347322, NCI-TCGA Cosmic COSV1012, cosmic curated COSV10127, gnomAD rs1238347322, CADD 38.00, Variant assessed as somatic; high impact.
- W46L (p.Trp46Leu), gnomAD 2-49926372-C-A, CADD 1.73, SIFT 0.39
- W46R (p.Trp46Arg), rs1669108000, gnomAD 2-49926373-A-T, CADD 1.02, SIFT 0.06
- N47N (p.Asn47Asn), rs754080263, gnomAD 2-49973974-G-A, CADD 18.80
- N47S (p.Asn47Ser), gnomAD 2-49973975-T-C, CADD 20.30, SIFT 0.90
- A48G (p.Ala48Gly), rs1202743952, ClinGen CA346824613, ClinVar RCV001209681, ClinVar RCV004792799, REVEL 0.51, CADD 23.50, Uncertain significance, Pitt-Hopkins-like syndrome 2; not provided
- A48T (p.Ala48Thr), rs1456330432, cosmic curated COSV10606, TOPMed rs1456330432, gnomAD rs1456330432, REVEL 0.59, CADD 23.90, Variant assessed as somatic; moderate impact.
- A48V (p.Ala48Val), NCI-TCGA TCGA novel, TOPMed rs1202743952, gnomAD rs1202743952, CADD 18.90, Uncertain significance
- C50S (p.Cys50Ser), NCI-TCGA Cosmic COSV6800, cosmic curated COSV68005, Variant assessed as somatic; moderate impact.
- C50W (p.Cys50Trp), rs1057518563, ClinGen CA16042428, ClinVar RCV000413417, TOPMed rs1057518563, REVEL 0.54, CADD 22.90, Uncertain significance, not specified
- C50Y (p.Cys50Tyr), NCI-TCGA TCGA novel, REVEL 0.52, CADD 22.90, Variant assessed as somatic; moderate impact.
- E51* (p.Glu51Ter), cosmic curated COSV68013, CADD 38.00
- E51K (p.Glu51Lys), cosmic curated COSV10750, REVEL 0.52, CADD 22.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- E51Q (p.Glu51Gln), gnomAD rs1670896275, REVEL 0.47, CADD 23.20
- S52R (p.Ser52Arg), NCI-TCGA Cosmic COSV6803, REVEL 0.61, CADD 24.30, Variant assessed as somatic; moderate impact.
- S52T (p.Ser52Thr), ExAC rs201059384, gnomAD rs201059384, REVEL 0.54, CADD 23.30, Uncertain significance, Pitt-Hopkins-like syndrome 2
- S52Y (p.Ser52Tyr), rs2104085266, gnomAD 2-49926363-G-T, CADD 3.71
- E53A (p.Glu53Ala), rs1287837969, ClinGen CA346824578, ClinVar RCV001063641, TOPMed rs1287837969, REVEL 0.59, CADD 23.20, Uncertain significance, Pitt-Hopkins-like syndrome 2
- E53K (p.Glu53Lys), rs1323402886, ClinGen CA346824580, ClinVar RCV001242849, TOPMed rs1323402886, REVEL 0.64, CADD 24.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- E53Q (p.Glu53Gln), TOPMed rs1323402886, gnomAD rs1323402886, REVEL 0.53, CADD 23.50, Uncertain significance
- E53E (p.Glu53Glu), rs1425704928, gnomAD 2-49926326-C-T, CADD 2.83
- M54I (p.Met54Ile), rs1057519409, ClinGen CA16044393, ClinVar RCV000417111, ClinVar RCV002521498, REVEL 0.34, CADD 21.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- M54L (p.Met54Leu), rs2105333796, ClinGen CA346824572, ClinVar RCV002051294, Ensembl rs2105333796, REVEL 0.23, CADD 15.60, Uncertain significance, Pitt-Hopkins-like syndrome 2
- M54R (p.Met54Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M54T (p.Met54Thr), gnomAD 2-49926375-A-G, CADD 6.16, SIFT 0.26
- S55G (p.Ser55Gly), Ensembl rs1670893180, REVEL 0.81, CADD 27.50
- S55T (p.Ser55Thr), rs2105333752, ClinGen CA346824561, ClinVar RCV001964745, Ensembl rs2105333752, REVEL 0.61, CADD 22.80, Uncertain significance, Pitt-Hopkins-like syndrome 2
- Q57P (p.Gln57Pro), Ensembl rs1670892046
- L58F (p.Leu58Phe), TOPMed rs1017563126, gnomAD rs1017563126, REVEL 0.21, CADD 19.20
- L58R (p.Leu58Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L58V (p.Leu58Val), TOPMed rs1017563126, gnomAD rs1017563126, REVEL 0.44, CADD 23.20
- K59R (p.Lys59Arg), rs1311818932, ClinGen CA346824529, ClinVar RCV001302313, ClinVar RCV003106187, REVEL 0.23, CADD 22.30, Uncertain significance, not provided; Pitt-Hopkins-like syndrome 2
- K59N (p.Lys59Asn), gnomAD 2-49926320-C-A, CADD 0.98
- K59K (p.Lys59Lys), rs1342281940, gnomAD 2-49926320-C-T, CADD 1.08
- T60I (p.Thr60Ile), cosmic curated COSV68037, REVEL 0.90, CADD 26.00
- T60N (p.Thr60Asn), cosmic curated COSV68019, REVEL 0.79, CADD 25.40
- R61C (p.Arg61Cys), NCI-TCGA Cosmic COSV6800, cosmic curated COSV68006, REVEL 0.58, CADD 29.40, Uncertain significance, not provided
- R61G (p.Arg61Gly), gnomAD rs1444822946, REVEL 0.43, CADD 23.10
- R61H (p.Arg61His), rs202205785, ExAC rs202205785, gnomAD rs202205785, REVEL 0.25, CADD 23.00, Variant assessed as somatic; moderate impact.
- R61L (p.Arg61Leu), ExAC rs202205785, gnomAD rs202205785, REVEL 0.45, CADD 23.00
- R61P (p.Arg61Pro), ExAC rs202205785, gnomAD rs202205785, REVEL 0.47, CADD 23.30
- R61K (p.Arg61Lys), rs1669101718, gnomAD 2-49926322-TCC-T, CADD 0.67
- R61R (p.Arg61Arg), rs990511144, gnomAD 2-49926323-C-T, CADD 0.74
- R61S (p.Arg61Ser), gnomAD 2-49926323-C-A, CADD 1.53
- R61W (p.Arg61Trp), gnomAD 2-49926325-T-A, CADD 0.56
- R61E (p.Arg61Glu), gnomAD 2-49926330-CTT-C, CADD 0.17
- R61I (p.Arg61Ile), rs1669103626, gnomAD 2-49926333-C-A, CADD 4.26
- S62C (p.Ser62Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S62R (p.Ser62Arg), rs1186547259, ClinGen CA346824507, ClinVar RCV002024512, TOPMed rs1186547259, REVEL 0.35, CADD 15.00, Uncertain significance, Pitt-Hopkins-like syndrome 2
- S62T (p.Ser62Thr), TOPMed rs1476357524, gnomAD rs1476357524, REVEL 0.46, CADD 18.00
- A63S (p.Ala63Ser), ExAC rs747724604, gnomAD rs747724604, REVEL 0.27, CADD 16.40
- A63T (p.Ala63Thr), cosmic curated COSV68001, ExAC rs747724604, gnomAD rs747724604, REVEL 0.21, CADD 20.70
- A63V (p.Ala63Val), rs1007566859, ClinGen CA48054935, ClinVar RCV001758909, ClinVar RCV002540653, REVEL 0.36, CADD 21.90, Uncertain significance, not provided; Pitt-Hopkins-like syndrome 2; Inborn genetic diseases
- A63G (p.Ala63Gly), gnomAD 2-49926336-G-C, CADD 4.00
- R64C (p.Arg64Cys), rs201566733, ClinGen CA1655550, NCI-TCGA Cosmic COSV6800, cosmic curated COSV68006, REVEL 0.58, CADD 25.30, Uncertain significance, Pitt-Hopkins-like syndrome 2
- R64G (p.Arg64Gly), ExAC rs201566733, TOPMed rs201566733, gnomAD rs201566733, REVEL 0.48, CADD 21.20, Likely benign
- R64H (p.Arg64His), rs200247365, NCI-TCGA Cosmic COSV1012, cosmic curated COSV10127, TOPMed rs200247365, REVEL 0.27, CADD 22.50, Variant assessed as somatic; moderate impact.
- R64S (p.Arg64Ser), rs201566733, ClinGen CA48054934, ClinVar RCV000649737, ClinVar RCV001565881, REVEL 0.21, CADD 18.20, Conflicting interpretations, Inborn genetic diseases; Pitt-Hopkins-like syndrome 2; not provided
- G65A (p.Gly65Ala), rs1670884089, ClinGen CA346824496, ClinVar RCV002045427, Ensembl rs1670884089, AlphaMissense 0.57, MetaLR 0.66, Uncertain significance, Pitt-Hopkins-like syndrome 2
- G65D (p.Gly65Asp), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10127, Ensembl rs1670884089, REVEL 0.84, AlphaMissense 0.57, Uncertain significance
- G65S (p.Gly65Ser), rs1404175088, NCI-TCGA Cosmic COSV6802, cosmic curated COSV68022, TOPMed rs1404175088, REVEL 0.79, CADD 24.40, Variant assessed as somatic; moderate impact.
- V67G (p.Val67Gly), NCI-TCGA Cosmic COSV1012, cosmic curated COSV10127, Variant assessed as somatic; moderate impact.
Public NRXN1 analysis runs
- NRXN1 analysis run — NRXN1 (3,001 variants) — completed 2026-08-19