SCN9A (Q15858) variants and mutations
SCN9A (also known as Q15858) is a human protein-coding gene encoding a sodium channel protein type 9 subunit alpha protein. The protein forms Nav1.7, a voltage-gated sodium channel that amplifies electrical signals in peripheral sensory neurons. Changes in Nav1.7 activity can produce either excessive pain or congenital insensitivity to pain, making SCN9A central to pain biology. This analysis covers 4,096 SCN9A variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes primary erythermalgia, paroxysmal extreme pain disorder, and channelopathy-associated congenital insensitivity to pain, autosomal recessive. Example SCN9A variants include M1?, A2S, and A2T.
Variant analysis overview
- Gene: SCN9A
- Protein: Q15858
- UniProt accession: Q15858
- Organism: Homo sapiens
- Variants analyzed: 4096
- Variant scope: all variants
- Completed: 2026-07-23
Variant and mutation evidence
- Variant composition: 3,699 unspecified-consequence records; 30 frameshift variants; 165 missense variants; 180 synonymous variants; 4 in-frame insertions; 6 stop-gained variants; 5 in-frame deletions; 6 substitution
- Prediction scores: 3,120 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: primary erythermalgia, paroxysmal extreme pain disorder, channelopathy-associated congenital insensitivity to pain, autosomal recessive, hereditary sensory and autonomic neuropathy type 2, epilepsy, Seizure, Channelopathy-associated congenital insensitivity to pain, Pain, bipolar disorder, hereditary sensory and autonomic neuropathy, major depressive disorder, Lennox-Gastaut syndrome.
Protein structure and variant hotspots
- Protein features: 24 transmembrane segments; 1 domains; 6 post-translational modification sites.
- Structural context: 1,020 variants have structural context.
- PTM context: 14 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 SCN9A variants
Examples include M1?, A2S, A2T, A2V, M3I, M3K, M3L, L4*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV57613
- A2S (p.Ala2Ser), ESP rs199841742, TOPMed rs199841742, gnomAD rs199841742, MetaLR 0.81, MetaSVM 0.52, Uncertain significance
- A2T (p.Ala2Thr), rs199841742, ClinGen CA59810489, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.81, MetaSVM 0.52, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- A2V (p.Ala2Val), rs2468155894, ClinGen CA349096308, ClinVar RCV002942214, NCI-TCGA TCGA novel, MetaLR 0.85, MetaSVM 0.88, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- M3I (p.Met3Ile), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57618, Variant assessed as somatic; moderate impact.
- M3K (p.Met3Lys), rs774249327, ClinGen CA1944909, cosmic curated COSV57611, ClinVar RCV001059309, MetaLR 0.69, MetaSVM -0.10, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- M3L (p.Met3Leu), cosmic curated COSV57613, MetaLR 0.71, MetaSVM 0.09
- L4* (p.Leu4Ter), Ensembl rs1553498123
- L4F (p.Leu4Phe), cosmic curated COSV57598, TOPMed rs1413327507, MetaLR 0.89, MetaSVM 0.89, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P5H (p.Pro5His), NCI-TCGA Cosmic COSV5761, NCI-TCGA Cosmic COSV5762, cosmic curated COSV57629, MetaLR 0.78, MetaSVM 0.46, Variant assessed as somatic; moderate impact.
- P5L (p.Pro5Leu), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57612, NCI-TCGA Cosmic COSV5762, MetaLR 0.59, MetaSVM -0.18, Variant assessed as somatic; moderate impact.
- P5T (p.Pro5Thr), rs201999985, ClinGen CA1944908, ClinVar RCV001201495, ClinVar RCV003992461, MetaLR 0.67, MetaSVM 0.14, Uncertain significance, Primary erythromelalgia; Paroxysmal extreme pain disorder; Channelopathy-associa
- P6L (p.Pro6Leu), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57619, MetaLR 0.94, MetaSVM 1.06, Variant assessed as somatic; moderate impact.
- P6S (p.Pro6Ser), cosmic curated COSV57626, MetaLR 0.93, MetaSVM 1.05
- P7A (p.Pro7Ala), ExAC rs749215366, gnomAD rs749215366, MetaLR 0.90, MetaSVM 0.98, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P7L (p.Pro7Leu), rs773012423, ClinGen CA1944906, ClinVar RCV001049049, ClinVar RCV002261262, AlphaMissense 0.43, MetaLR 0.90, Uncertain significance, not provided; Neuropathy, hereditary sensory and autonomic, type 2A; Generalized
- P7Q (p.Pro7Gln), rs773012423, NCI-TCGA TCGA novel, ClinGen CA349096279, ClinVar RCV002036428, AlphaMissense 0.43, MetaLR 0.90, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P7R (p.Pro7Arg), rs773012423, ClinGen CA349096278, ClinVar RCV002272106, ExAC rs773012423, AlphaMissense 0.43, MetaLR 0.90, Uncertain significance, not provided
- P7S (p.Pro7Ser), ExAC rs749215366, gnomAD rs749215366, MetaLR 0.92, MetaSVM 1.05
- G8* (p.Gly8Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G8A (p.Gly8Ala), rs747772882, ClinGen CA1944904, ClinVar RCV000554062, ClinVar RCV004024171, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G8E (p.Gly8Glu), cosmic curated COSV10732, MetaLR 0.93, MetaSVM 1.04
- G8R (p.Gly8Arg), ExAC rs769491361, gnomAD rs769491361, MetaLR 0.96, MetaSVM 1.10
- P9F (p.Pro9Phe), cosmic curated COSV57624
- P9H (p.Pro9His), cosmic curated COSV57627
- P9L (p.Pro9Leu), Ensembl rs1698968936, MetaLR 0.90, MetaSVM 1.03
- P9T (p.Pro9Thr), TOPMed rs1698969032
- Q10* (p.Gln10Ter), cosmic curated COSV57607, ExAC rs781060177, gnomAD rs781060177
- Q10E (p.Gln10Glu), ExAC rs781060177, gnomAD rs781060177, MetaLR 0.48, MetaSVM -0.17
- Q10H (p.Gln10His), rs942556763, ClinGen CA59810469, ClinVar RCV001053954, TOPMed rs942556763, MetaLR 0.65, MetaSVM -0.05, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- Q10R (p.Gln10Arg), rs267607030, ClinGen CA253850, cosmic curated COSV10031, ClinVar RCV000006742, MetaLR 0.69, MetaSVM 0.32, Likely benign, Primary erythromelalgia; Generalized epilepsy with febrile seizures plus, type 7
- S11N (p.Ser11Asn), rs1347545350, ClinGen CA349096259, cosmic curated COSV57606, ClinVar RCV003785824, MetaLR 0.87, MetaSVM 0.81, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- V13F (p.Val13Phe), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57613, Variant assessed as somatic; moderate impact.
- V13I (p.Val13Ile), rs779738791, ClinGen CA349096246, ClinVar RCV001042146, ClinVar RCV002481893, MetaLR 0.78, MetaSVM 0.24, Uncertain significance, Primary erythromelalgia; Neuropathy, hereditary sensory and autonomic, type 2A
- V13L (p.Val13Leu), ExAC rs779738791, gnomAD rs779738791, MetaLR 0.79, MetaSVM 0.25, Uncertain significance
- H14P (p.His14Pro), rs201000497, ClinGen CA59810463, ClinVar RCV001370238, TOPMed rs201000497, MetaLR 0.37, MetaSVM -0.35, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- H14R (p.His14Arg), rs201000497, ClinGen CA349096237, ClinVar RCV003790203, TOPMed rs201000497, MetaLR 0.37, MetaSVM -0.46, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- H14Y (p.His14Tyr), cosmic curated COSV10514
- F15L (p.Phe15Leu), ExAC rs758888190, gnomAD rs758888190, MetaLR 0.97, MetaSVM 1.09
- T16P (p.Thr16Pro), Ensembl rs2105227248, MetaLR 0.97, MetaSVM 1.19
- K17* (p.Lys17Ter), 1000Genomes rs181981693, ExAC rs181981693, TOPMed rs181981693, gnomAD rs181981693, Uncertain significance
- K17E (p.Lys17Glu), rs181981693, ClinGen CA1944899, cosmic curated COSV10031, ClinVar RCV001052029, MetaLR 0.68, MetaSVM -0.09, Uncertain significance, Inborn genetic diseases; Neuropathy, hereditary sensory and autonomic, type 2A
- Q18* (p.Gln18Ter), gnomAD rs1391453280, CADD 36.00
- Q18H (p.Gln18His), rs1404773417, ClinGen CA349096208, ClinVar RCV001057829, TOPMed rs1404773417, MetaLR 0.84, MetaSVM 0.80, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- Q18L (p.Gln18Leu), rs1319079239, ClinGen CA349096211, ClinVar RCV002050940, TOPMed rs1319079239, MetaLR 0.82, MetaSVM 0.78, Uncertain significance
- Q18R (p.Gln18Arg), TOPMed rs1319079239, gnomAD rs1319079239, MetaLR 0.79, MetaSVM 0.50, Uncertain significance
- L20F (p.Leu20Phe), rs200056934, ClinGen CA1944898, cosmic curated COSV57604, ClinVar RCV000538259, MetaLR 0.95, MetaSVM 1.10, Uncertain significance, Inborn genetic diseases; Neuropathy, hereditary sensory and autonomic, type 2A
- L20P (p.Leu20Pro), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Variant assessed as somatic; moderate impact.
- L20R (p.Leu20Arg), rs757627939, ClinGen CA1944897, ClinVar RCV002261697, ExAC rs757627939, MetaLR 0.97, MetaSVM 1.08, Uncertain significance, not provided
- A21S (p.Ala21Ser), NCI-TCGA TCGA novel, MetaLR 0.94, MetaSVM 1.04, Variant assessed as somatic; moderate impact.
- A21V (p.Ala21Val), rs1458587448, ClinGen CA349096191, ClinVar RCV001326576, gnomAD rs1458587448, MetaLR 0.82, MetaSVM 0.46, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- L22F (p.Leu22Phe), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- L22P (p.Leu22Pro), rs754046765, ClinGen CA349096187, ClinVar RCV001215036, ExAC rs754046765, MetaLR 0.72, MetaSVM 0.05, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- L22R (p.Leu22Arg), cosmic curated COSV57627, ExAC rs754046765, Uncertain significance
- L22V (p.Leu22Val), rs978057086, ClinGen CA59810446, ClinVar RCV000794902, ClinVar RCV004027507, MetaLR 0.70, MetaSVM 0.02, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- I23F (p.Ile23Phe), rs2105227146, ClinGen CA349096184, ClinVar RCV003791669, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- I23L (p.Ile23Leu), rs2105227146, ClinGen CA349096186, ClinVar RCV001977388, Ensembl rs2105227146, MetaLR 0.91, MetaSVM 0.92, Uncertain significance
- I23N (p.Ile23Asn), rs1389373425, ClinGen CA349096181, ClinVar RCV000804385, ClinVar RCV006367362, MetaLR 0.97, MetaSVM 1.09, Uncertain significance, Inborn genetic diseases; Neuropathy, hereditary sensory and autonomic, type 2A
- I23T (p.Ile23Thr), rs1389373425, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, 1000Genomes rs1389373425, MetaLR 0.95, MetaSVM 1.09, Uncertain significance
- E24* (p.Glu24Ter), Ensembl rs1553498086
- E24K (p.Glu24Lys), cosmic curated COSV10514
- Q25* (p.Gln25Ter), ESP rs200709311, ExAC rs200709311, TOPMed rs200709311, gnomAD rs200709311, Uncertain significance
- Q25K (p.Gln25Lys), rs200709311, ClinGen CA1944894, ClinVar RCV001133440, ClinVar RCV001133441, MetaLR 0.56, MetaSVM -0.12, Uncertain significance, Primary erythromelalgia; Neuropathy, hereditary sensory and autonomic, type 2A
- R26C (p.Arg26Cys), rs199933920, ClinGen CA1944893, cosmic curated COSV57614, ClinVar RCV000236265, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- R26H (p.Arg26His), rs111404258, ClinGen CA1944892, cosmic curated COSV10646, ClinVar RCV001066731, MetaLR 0.95, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- R26L (p.Arg26Leu), rs111404258, ClinGen CA349096162, ClinVar RCV002700583, ExAC rs111404258, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- R26P (p.Arg26Pro), rs111404258, ClinGen CA59810435, ClinVar RCV001340703, ExAC rs111404258, MetaLR 0.97, MetaSVM 1.09, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- I27T (p.Ile27Thr), gnomAD rs1291370045, MetaLR 0.91, MetaSVM 1.03
- I27V (p.Ile27Val), TOPMed rs1449322124, gnomAD rs1449322124, MetaLR 0.90, MetaSVM 0.92, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- A28V (p.Ala28Val), gnomAD rs1698965479, MetaLR 0.91, MetaSVM 0.92, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- E29* (p.Glu29Ter), gnomAD rs1210104999, AlphaMissense 0.09, MetaLR 0.94
- E29K (p.Glu29Lys), rs1210104999, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, gnomAD rs1210104999, AlphaMissense 0.09, MetaLR 0.94, Variant assessed as somatic; moderate impact.
- R30* (p.Arg30Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K31* (p.Lys31Ter), Ensembl rs1553498068
- K31I (p.Lys31Ile), rs920979487, ClinGen CA59810432, ClinVar RCV001975679, ClinVar RCV003250366, MetaLR 0.92, MetaSVM 1.09, Uncertain significance
- S32* (p.Ser32Ter), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, CADD 35.00, Variant assessed as somatic; high impact.
- S32L (p.Ser32Leu), cosmic curated COSV10588, MetaLR 0.36, MetaSVM -0.34
- S32T (p.Ser32Thr), rs2105227008, ClinGen CA349096126, ClinVar RCV002035084, ClinVar RCV004693788, MetaLR 0.69, MetaSVM -0.19, Uncertain significance
- K33* (p.Lys33Ter), Ensembl rs1553498063
- K33N (p.Lys33Asn), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57617, Ensembl rs1698964789, Variant assessed as somatic; moderate impact.
- K33R (p.Lys33Arg), rs2468155085, ClinGen CA349096116, ClinVar RCV002975686, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- E34* (p.Glu34Ter), TOPMed rs1274442703, gnomAD rs1274442703, CADD 34.00, Uncertain significance
- E34K (p.Glu34Lys), rs1274442703, ClinGen CA349096112, NCI-TCGA Cosmic COSV5761, NCI-TCGA Cosmic COSV5762, MetaLR 0.45, MetaSVM -0.39, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- E34Q (p.Glu34Gln), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57612, NCI-TCGA Cosmic COSV5762, MetaLR 0.63, MetaSVM -0.27, Variant assessed as somatic; moderate impact.
- P35H (p.Pro35His), rs1367983811, NCI-TCGA Cosmic COSV5760, cosmic curated COSV57604, TOPMed rs1367983811, MetaLR 0.85, MetaSVM 0.20, Variant assessed as somatic; moderate impact.
- P35T (p.Pro35Thr), ExAC rs762892329, gnomAD rs762892329, MetaLR 0.82, MetaSVM 0.15, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- K36* (p.Lys36Ter), Ensembl rs1553498059
- K36Q (p.Lys36Gln), cosmic curated COSV10440
- E37* (p.Glu37Ter), Ensembl rs1553498056
- E37K (p.Glu37Lys), cosmic curated COSV57612
- E38* (p.Glu38Ter), TOPMed rs1553498053
- E38G (p.Glu38Gly), rs974242226, ClinGen CA59810423, ClinVar RCV002261696, TOPMed rs974242226, MetaLR 0.85, MetaSVM 0.66, Uncertain significance, not provided
- E38K (p.Glu38Lys), NCI-TCGA Cosmic COSV5761, cosmic curated COSV57617, Variant assessed as somatic; moderate impact.
- K39* (p.Lys39Ter), Ensembl rs1553498033
- K39N (p.Lys39Asn), rs1574913597, ClinGen CA349096070, ClinVar RCV000813833, Ensembl rs1574913597, MetaLR 0.70, MetaSVM 0.33, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- K39R (p.Lys39Arg), rs773030286, ClinGen CA1944889, ClinVar RCV002010590, ExAC rs773030286, MetaLR 0.66, MetaSVM -0.39, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- K40* (p.Lys40Ter), ESP rs371565974, ExAC rs371565974, gnomAD rs371565974, Uncertain significance
- K40E (p.Lys40Glu), rs371565974, ClinGen CA1944888, ClinVar RCV000698918, ClinVar RCV002261189, MetaLR 0.71, MetaSVM 0.03, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D41G (p.Asp41Gly), rs368147111, ClinGen CA1944886, ClinVar RCV003796802, ESP rs368147111, MetaLR 0.81, MetaSVM 0.60, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D41H (p.Asp41His), 1000Genomes rs529727269, ExAC rs529727269, TOPMed rs529727269, gnomAD rs529727269, AlphaMissense 0.13, MetaLR 0.92, Uncertain significance
- D41N (p.Asp41Asn), rs529727269, ClinGen CA349096061, ClinVar RCV001317761, 1000Genomes rs529727269, AlphaMissense 0.13, MetaLR 0.92, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D41Y (p.Asp41Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D42E (p.Asp42Glu), rs371884028, ClinGen CA349096050, ClinVar RCV000647765, ESP rs371884028, AlphaMissense 0.09, MetaLR 0.71, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D42G (p.Asp42Gly), rs373650798, ClinGen CA349096052, ClinVar RCV003024157, AlphaMissense 0.09, MetaLR 0.89, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D42V (p.Asp42Val), rs373650798, ClinGen CA1944885, ClinVar RCV002929050, ESP rs373650798, AlphaMissense 0.09, MetaLR 0.89, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D42Y (p.Asp42Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D43E (p.Asp43Glu), ESP rs200826539, ExAC rs200826539, gnomAD rs200826539, MetaLR 0.40, MetaSVM -0.34, Benign
- D43N (p.Asp43Asn), rs866960803, ClinGen CA59810405, ClinVar RCV003804985, Ensembl rs866960803, AlphaMissense 0.07, MetaLR 0.83, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- E44* (p.Glu44Ter), ExAC rs757848676, gnomAD rs757848676, Uncertain significance
- E44K (p.Glu44Lys), rs757848676, ClinGen CA1944882, ClinVar RCV003386064, ExAC rs757848676, MetaLR 0.90, MetaSVM 0.89, Uncertain significance, Inborn genetic diseases
- E44Q (p.Glu44Gln), ExAC rs757848676, gnomAD rs757848676, MetaLR 0.94, MetaSVM 1.08, Uncertain significance
- E44V (p.Glu44Val), ExAC rs746381295, gnomAD rs746381295, MetaLR 0.88, MetaSVM 0.85
- E45* (p.Glu45Ter), rs1553498017, ClinGen CA349096034, ClinVar RCV000802937, Ensembl rs1553498017, CADD 34.00, Pathogenic
- E45K (p.Glu45Lys), cosmic curated COSV10588, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- A46G (p.Ala46Gly), TOPMed rs1698962097, gnomAD rs1698962097, MetaLR 0.37, MetaSVM -0.50, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- A46T (p.Ala46Thr), rs779344629, ClinGen CA1944880, ClinVar RCV000235355, ClinVar RCV000533794, MetaLR 0.75, MetaSVM 0.09, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P47L (p.Pro47Leu), cosmic curated COSV10031
- P47Q (p.Pro47Gln), rs1281216048, NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; high impact.
- K48E (p.Lys48Glu), rs2105226773, ClinGen CA349096016, ClinVar RCV001893986, Ensembl rs2105226773, AlphaMissense 0.13, MetaLR 0.88, Uncertain significance
- P49A (p.Pro49Ala), ExAC rs778143440, gnomAD rs778143440
- P49Q (p.Pro49Gln), Ensembl rs1698961608
- P49S (p.Pro49Ser), ExAC rs778143440, gnomAD rs778143440, MetaLR 0.96, MetaSVM 1.10
- P49T (p.Pro49Thr), ExAC rs778143440, gnomAD rs778143440, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- S50R (p.Ser50Arg), gnomAD rs1344699520, MetaLR 0.66, MetaSVM 0.10
- S50T (p.Ser50Thr), rs2468154542, ClinGen CA349096000, ClinVar RCV003785245, MetaLR 0.76, MetaSVM 0.57, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- S51G (p.Ser51Gly), Ensembl rs2105226738, MetaLR 0.66, MetaSVM -0.51
- S51R (p.Ser51Arg), rs199836776, ClinGen CA1944876, ClinVar RCV000493139, ClinVar RCV000647811, MetaLR 0.66, MetaSVM -0.51, Conflicting interpretations, Inborn genetic diseases; not specified; Neuropathy, hereditary sensory and auton
- E54* (p.Glu54Ter), Ensembl rs895331828
- E54K (p.Glu54Lys), Ensembl rs895331828, MetaLR 0.89, MetaSVM 0.91
- A55D (p.Ala55Asp), rs1222851635, ClinGen CA349095963, ClinVar RCV000705708, TOPMed rs1222851635, AlphaMissense 0.85, MetaLR 0.94, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- A55G (p.Ala55Gly), rs1222851635, ClinGen CA349095962, ClinVar RCV003023215, AlphaMissense 0.85, MetaLR 0.94, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- A55P (p.Ala55Pro), rs2468154451, ClinGen CA349095967, ClinVar RCV003032668, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G56C (p.Gly56Cys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Variant assessed as somatic; moderate impact.
- G56D (p.Gly56Asp), ExAC rs767568953, gnomAD rs767568953, MetaLR 0.97, MetaSVM 1.08, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G56S (p.Gly56Ser), TOPMed rs1698961116
- K57* (p.Lys57Ter), Ensembl rs201061055
- K57Q (p.Lys57Gln), Ensembl rs201061055, MetaLR 0.85, MetaSVM 0.51
- K57R (p.Lys57Arg), TOPMed rs1288637616, gnomAD rs1288637616, MetaLR 0.88, MetaSVM 0.92, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- Q58* (p.Gln58Ter), ExAC rs759604608, gnomAD rs759604608, CADD 35.00
- Q58H (p.Gln58His), 1000Genomes rs6432901, ESP rs6432901, ExAC rs6432901, TOPMed rs6432901, MetaLR 0.80, MetaSVM 0.67, Benign
- L59Q (p.Leu59Gln), NCI-TCGA TCGA novel, MetaLR 0.98, MetaSVM 1.05, Variant assessed as somatic; moderate impact.
- P60L (p.Pro60Leu), cosmic curated COSV57624, MetaLR 0.99, MetaSVM 1.00, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P60R (p.Pro60Arg), rs1574913467, ClinGen CA349095934, ClinVar RCV000819635, Ensembl rs1574913467, AlphaMissense 0.88, MetaLR 0.99, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- P60S (p.Pro60Ser), 1000Genomes rs540853945, ExAC rs540853945, MetaLR 0.99, MetaSVM 1.02, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- F61Y (p.Phe61Tyr), rs1698959890, ClinGen CA349095929, ClinVar RCV001060250, ClinVar RCV002553878, AlphaMissense 0.18, MetaLR 0.84, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- I62N (p.Ile62Asn), TOPMed rs886681700, gnomAD rs886681700, MetaLR 0.95, MetaSVM 1.10, Uncertain significance
- I62T (p.Ile62Thr), rs886681700, ClinGen CA59810371, ClinVar RCV001236880, TOPMed rs886681700, MetaLR 0.95, MetaSVM 1.10, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- I62V (p.Ile62Val), rs121908920, ClinGen CA118170, ClinVar RCV000006740, ClinVar RCV000215091, MetaLR 0.92, MetaSVM 1.09, Uncertain significance, not provided; Generalized epilepsy with febrile seizures plus, type 7; Neuropath
- Y63C (p.Tyr63Cys), rs1698959401, ClinGen CA349095916, ClinVar RCV001208251, TOPMed rs1698959401, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- Y63H (p.Tyr63His), gnomAD rs1698959487, AlphaMissense 0.81, MetaLR 0.95
- Y63N (p.Tyr63Asn), rs1698959487, ClinGen CA349095919, ClinVar RCV002613010, AlphaMissense 0.81, MetaLR 0.95, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G64A (p.Gly64Ala), rs558889724, ClinGen CA349095909, ClinVar RCV001059784, 1000Genomes rs558889724, AlphaMissense 0.43, MetaLR 0.96, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- G64E (p.Gly64Glu), rs558889724, ClinGen CA349095908, ClinVar RCV003794793, AlphaMissense 0.43, MetaLR 0.96, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G64R (p.Gly64Arg), cosmic curated COSV57625
- G64V (p.Gly64Val), 1000Genomes rs558889724, ExAC rs558889724, TOPMed rs558889724, gnomAD rs558889724, AlphaMissense 0.43, MetaLR 0.96, Uncertain significance
- D65E (p.Asp65Glu), rs2468154101, ClinGen CA349095900, ClinVar RCV003804030, MetaLR 0.77, MetaSVM 0.48, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D65N (p.Asp65Asn), rs1281452286, ClinGen CA349095907, ClinVar RCV002796466, ClinVar RCV004064876, MetaLR 0.86, MetaSVM 0.80, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- D65V (p.Asp65Val), NCI-TCGA TCGA novel, MetaLR 0.95, MetaSVM 1.09, Variant assessed as somatic; high impact.
- D65Y (p.Asp65Tyr), TOPMed rs1281452286, gnomAD rs1281452286, Uncertain significance
- I66L (p.Ile66Leu), Ensembl rs1574913413
- I66T (p.Ile66Thr), rs2468154056, ClinGen CA349095896, ClinVar RCV003809947, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P67A (p.Pro67Ala), gnomAD rs1354932910, MetaLR 0.97, MetaSVM 1.09, Uncertain significance
- P67S (p.Pro67Ser), rs1354932910, ClinGen CA349095890, ClinVar RCV001371786, ClinVar RCV002420836, MetaLR 0.96, MetaSVM 1.10, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P67T (p.Pro67Thr), gnomAD rs1354932910, MetaLR 0.97, MetaSVM 1.09, Uncertain significance
- P68S (p.Pro68Ser), rs1333258106, ClinGen CA349095884, cosmic curated COSV57623, ClinVar RCV003069556, MetaLR 0.78, MetaSVM 0.41, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G69C (p.Gly69Cys), ESP rs201243874, ExAC rs201243874, TOPMed rs201243874, gnomAD rs201243874, MetaLR 0.92, MetaSVM 0.83, Uncertain significance
- G69R (p.Gly69Arg), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, ESP rs201243874, ExAC rs201243874, MetaLR 0.78, MetaSVM 0.39, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- G69S (p.Gly69Ser), rs201243874, ClinGen CA1944868, cosmic curated COSV10459, ClinVar RCV000647798, MetaLR 0.81, MetaSVM 0.42, Uncertain significance, Inborn genetic diseases; Neuropathy, hereditary sensory and autonomic, type 2A
- G69V (p.Gly69Val), NCI-TCGA Cosmic COSV5762, cosmic curated COSV57621, MetaLR 0.92, MetaSVM 1.03, Variant assessed as somatic; moderate impact.
- M70I (p.Met70Ile), rs1574913387, Ensembl rs1574913387, ClinGen CA349095869, ClinVar RCV001338510, MetaLR 0.88, MetaSVM 0.89, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- M70T (p.Met70Thr), rs1329565373, ClinGen CA349095871, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.86, MetaSVM 0.90, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- V71M (p.Val71Met), rs2468153911, ClinGen CA349095864, ClinVar RCV002613670, Uncertain significance, Generalized epilepsy with febrile seizures plus, type 7; Neuropathy, hereditary
- S72L (p.Ser72Leu), ExAC rs745418676, gnomAD rs745418676, MetaLR 0.92, MetaSVM 1.05
- E73* (p.Glu73Ter), cosmic curated COSV57598, gnomAD rs1409339552, Uncertain significance
- E73D (p.Glu73Asp), gnomAD rs1183962696, MetaLR 0.90, MetaSVM 0.95
- E73K (p.Glu73Lys), rs1409339552, ClinGen CA349095854, cosmic curated COSV10732, ClinVar RCV002963003, MetaLR 0.81, MetaSVM 0.69, Uncertain significance, Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with
- P74A (p.Pro74Ala), TOPMed rs1698957501
- P74H (p.Pro74His), TOPMed rs201992546, MetaLR 0.99, MetaSVM 1.02
- P74L (p.Pro74Leu), TOPMed rs201992546, MetaLR 0.98, MetaSVM 1.05
- P74T (p.Pro74Thr), TOPMed rs1698957501
Public SCN9A analysis runs
- SCN9A analysis run — SCN9A (4,096 variants) — completed 2026-07-23
- SCN9A analysis run — SCN9A (4,080 variants) — completed 2026-05-15