L1CAM (Neural cell adhesion molecule L1) variants and mutations
L1CAM (also known as Neural cell adhesion molecule L1) is a human protein-coding gene encoding a neural cell adhesion molecule L1 protein. It promotes neuronal adhesion, axon guidance, neurite growth, and fasciculation during nervous-system development. Loss-of-function variants cause L1 syndrome, encompassing X-linked hydrocephalus, MASA syndrome, spastic paraplegia, and variable intellectual disability. This analysis covers 1,359 L1CAM variants and mutations. Of these, 65% have computational variant effect predictions. Disease context includes Hydrocephalus with stenosis of the aqueduct of Sylvius, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, and MASA syndrome. Example L1CAM variants include M1I, M1V, and V2A.
Variant analysis overview
- Gene: L1CAM
- Protein: Neural cell adhesion molecule L1
- UniProt accession: P32004
- Organism: Homo sapiens
- Variants analyzed: 1359
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,189 unspecified-consequence records; 1 stop retained variant; 93 synonymous variants; 67 missense variants; 2 in-frame deletions; 5 splice-region variants; 5 substitution
- Prediction scores: 887 variants have prediction scores (65% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Hydrocephalus with stenosis of the aqueduct of Sylvius, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, MASA syndrome, X-linked complicated corpus callosum dysgenesis, L1 syndrome, Spastic paraplegia, hereditary disease, Partial agenesis of the corpus callosum, X-linked complicated spastic paraplegia type 1, neurodegenerative disease, hydrops fetalis, Severe hydrocephalus.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 11 domains; 29 post-translational modification sites.
- Structural context: 1,065 variants have structural context.
- PTM context: 29 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable L1CAM variants
Examples include M1I, M1V, V2A, A4T, A4V, R6P, R6W, Y7C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1603277433, ClinGen CA415143345, ClinVar RCV000990984, MetaLR 0.56, MetaSVM 0.18, Likely pathogenic, X-linked hydrocephalus syndrome
- M1V (p.Met1Val), rs2521057345, ClinGen CA415143360, ClinVar RCV002417110, Likely pathogenic, Inborn genetic diseases
- V2A (p.Val2Ala), NCI-TCGA Cosmic COSV6280, cosmic curated COSV62808, Variant assessed as somatic; moderate impact.
- A4T (p.Ala4Thr), ExAC rs782267074, gnomAD rs782267074, REVEL 0.09, CADD 19.00
- A4V (p.Ala4Val), 1000Genomes rs201284179, ExAC rs201284179, REVEL 0.09, CADD 18.20
- R6P (p.Arg6Pro), ExAC rs782609143, gnomAD rs782609143, REVEL 0.45, CADD 22.30
- R6W (p.Arg6Trp), rs2521057181, ClinGen CA415143217, ClinVar RCV003751816, REVEL 0.24, CADD 23.00, Uncertain significance, Spastic paraplegia
- Y7C (p.Tyr7Cys), rs2148502578, ClinGen CA415143186, ClinVar RCV003480417, Ensembl rs2148502578, REVEL 0.33, CADD 23.30, Uncertain significance, not provided
- V8E (p.Val8Glu), rs886044768, ClinGen CA10603776, ClinVar RCV000314558, Ensembl rs886044768, AlphaMissense 0.40, MetaLR 0.35, Uncertain significance, not provided
- V8L (p.Val8Leu), rs2064809371, Ensembl rs2064809371, ClinGen CA415143174, ClinVar RCV003751520, REVEL 0.05, CADD 10.40, Uncertain significance, not provided; Spastic paraplegia
- W9* (p.Trp9Ter), rs1557094409, ClinGen CA415143117, ClinVar RCV000657775, Ensembl rs1557094409, Pathogenic, in HYCX
- W9S (p.Trp9Ser), UniProt VAR 003921, Pathogenic, in HYCX
- P10A (p.Pro10Ala), 1000Genomes rs144605615, ESP rs144605615, ExAC rs144605615, TOPMed rs144605615, REVEL 0.10, CADD 18.70, Benign
- P10S (p.Pro10Ser), rs144605615, ClinGen CA146093, cosmic curated COSV99051, ClinVar RCV000078738, REVEL 0.10, CADD 19.20, Benign
- L11R (p.Leu11Arg), NCI-TCGA Cosmic COSV6280, cosmic curated COSV62808, Variant assessed as somatic; moderate impact.
- C14W (p.Cys14Trp), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- I20L (p.Ile20Leu), TOPMed rs1311732412, gnomAD rs1311732412, REVEL 0.27, CADD 23.40
- I20S (p.Ile20Ser), Ensembl rs2064808951
- I22M (p.Ile22Met), rs1557094388, ClinGen CA415142559, ClinVar RCV002006734, gnomAD rs1557094388, AlphaMissense 0.15, MetaLR 0.30, Uncertain significance, Spastic paraplegia
- I22V (p.Ile22Val), rs2064808887, ClinGen CA415142607, ClinVar RCV002601140, gnomAD rs2064808887, REVEL 0.18, CADD 23.10, Uncertain significance, Spastic paraplegia
- E24K (p.Glu24Lys), gnomAD rs1557094385, REVEL 0.09, CADD 14.10
- E24Q (p.Glu24Gln), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- E25=, NCI-TCGA Cosmic COSV1006, Variant assessed as somatic; low impact.
- E25K (p.Glu25Lys), TOPMed rs1335792529, gnomAD rs1335792529, REVEL 0.17, CADD 20.50
- Y26* (p.Tyr26Ter), rs2521043571, ClinGen CA415141915, ClinVar RCV003066410, Pathogenic
- E27A (p.Glu27Ala), gnomAD rs1557093757, REVEL 0.11, CADD 23.00, Likely benign, Spastic paraplegia
- G28* (p.Gly28Ter), TOPMed rs1557093752, gnomAD rs1557093752
- G28E (p.Gly28Glu), NCI-TCGA Cosmic COSV6282, REVEL 0.32, CADD 16.60, Variant assessed as somatic; moderate impact.
- G28R (p.Gly28Arg), cosmic curated COSV62829, TOPMed rs1557093752, gnomAD rs1557093752, REVEL 0.29, CADD 22.70
- H29R (p.His29Arg), ExAC rs782772477, TOPMed rs782772477, gnomAD rs782772477, REVEL 0.05, CADD 14.50
- H30N (p.His30Asn), UniProt VAR 030403
- V31A (p.Val31Ala), rs782476478, ClinGen CA10554665, ClinVar RCV003750828, ExAC rs782476478, REVEL 0.58, CADD 21.60, Benign, Spastic paraplegia
- E33D (p.Glu33Asp), rs201990980, ClinGen CA10554664, ClinVar RCV002381944, ClinVar RCV003586231, REVEL 0.23, CADD 19.90, Benign/Likely benign, Spastic paraplegia; Inborn genetic diseases
- P34L (p.Pro34Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V36I (p.Val36Ile), TOPMed rs2064783020, REVEL 0.02, CADD 12.90
- I37N (p.Ile37Asn), UniProt VAR 078351, Pathogenic, found in L1 syndrome
- T38M (p.Thr38Met), rs201151358, ClinGen CA10554662, ClinVar RCV000524706, ClinVar RCV001653889, REVEL 0.29, CADD 24.70, Benign/Likely benign, Spastic paraplegia; not specified; Inborn genetic diseases
- S41C (p.Ser41Cys), rs2521039021, ClinGen CA415140442, ClinVar RCV003487983, Uncertain significance, not provided
- S41Y (p.Ser41Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P42A (p.Pro42Ala), Ensembl rs2064782707
- P42L (p.Pro42Leu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- P42R (p.Pro42Arg), NCI-TCGA Cosmic COSV1006, Variant assessed as somatic; moderate impact.
- P42S (p.Pro42Ser), rs2064782707, ClinGen CA415140435, ClinVar RCV003482754, AlphaMissense 0.20, MetaLR 0.90, Uncertain significance, not provided
- R43L (p.Arg43Leu), ExAC rs782819951, gnomAD rs782819951, REVEL 0.18, CADD 20.30
- R43Q (p.Arg43Gln), cosmic curated COSV10064, ExAC rs782819951, gnomAD rs782819951, REVEL 0.10, CADD 20.60
- R43W (p.Arg43Trp), gnomAD rs1557093590, REVEL 0.43, CADD 25.00
- R44C (p.Arg44Cys), rs370782270, ClinGen CA10554658, ClinVar RCV001240369, ClinVar RCV002379917, REVEL 0.62, CADD 28.50, Uncertain significance, Inborn genetic diseases; Spastic paraplegia
- R44H (p.Arg44His), rs367644081, ClinGen CA10554657, ClinVar RCV003840859, ESP rs367644081, REVEL 0.38, CADD 23.60, Benign, Spastic paraplegia
- R44L (p.Arg44Leu), NCI-TCGA TCGA novel, REVEL 0.48, CADD 22.60, Variant assessed as somatic; moderate impact.
- R44S (p.Arg44Ser), ESP rs370782270, ExAC rs370782270, TOPMed rs370782270, gnomAD rs370782270, REVEL 0.33, CADD 20.10, Uncertain significance
- L45M (p.Leu45Met), rs370373282, ClinGen CA10554655, ClinVar RCV003992912, ESP rs370373282, REVEL 0.07, CADD 23.80, Likely benign, not provided
- V47A (p.Val47Ala), ESP rs143684296, ExAC rs143684296, TOPMed rs143684296, gnomAD rs143684296, REVEL 0.21, CADD 23.10, Uncertain significance, Spastic paraplegia
- V47F (p.Val47Phe), rs147251476, ClinGen CA10554654, ClinVar RCV002389219, ClinVar RCV003774305, REVEL 0.20, CADD 24.10, Conflicting interpretations, Inborn genetic diseases; Spastic paraplegia
- V47I (p.Val47Ile), ESP rs147251476, ExAC rs147251476, TOPMed rs147251476, gnomAD rs147251476, Benign
- P49S (p.Pro49Ser), rs1557093565, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, gnomAD rs1557093565, REVEL 0.16, CADD 22.90, Variant assessed as somatic; moderate impact.
- T50Q (p.Thr50Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- I53M (p.Ile53Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S54N (p.Ser54Asn), ExAC rs781924972, TOPMed rs781924972, gnomAD rs781924972
- C57Y (p.Cys57Tyr), rs1057517755, ClinGen CA16043181, ClinVar RCV000413431, Ensembl rs1057517755, AlphaMissense 0.99, MetaLR 0.95, Uncertain significance, not provided
- A59V (p.Ala59Val), rs2148500384, ClinGen CA415139930, ClinVar RCV001372486, Ensembl rs2148500384, AlphaMissense 0.66, MetaLR 0.10, Uncertain significance, Spastic paraplegia
- S60I (p.Ser60Ile), rs2521038376, ClinGen CA415139901, ClinVar RCV003046315, ClinVar RCV003236945, Conflicting interpretations, Spastic paraplegia; not provided
- G61V (p.Gly61Val), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- E64K (p.Glu64Lys), rs782092168, ClinGen CA10554650, ClinVar RCV003750762, ExAC rs782092168, REVEL 0.05, CADD 8.72, Likely benign, Spastic paraplegia
- E64Q (p.Glu64Gln), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- F67L (p.Phe67Leu), TOPMed rs1465205361, gnomAD rs1465205361, REVEL 0.41, CADD 28.80
- R68C (p.Arg68Cys), rs1172761444, ClinGen CA415139517, NCI-TCGA Cosmic COSV6282, cosmic curated COSV62829, REVEL 0.28, CADD 25.80, Conflicting interpretations, Spastic paraplegia; not provided
- R68H (p.Arg68His), Ensembl rs2064778846, REVEL 0.11, AlphaMissense 0.40, Uncertain significance
- R68L (p.Arg68Leu), rs2064778846, ClinGen CA415139469, ClinVar RCV001905603, Ensembl rs2064778846, AlphaMissense 0.40, MetaLR 0.06, Uncertain significance, Spastic paraplegia
- W69C (p.Trp69Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T70A (p.Thr70Ala), Ensembl rs200996065
- T70K (p.Thr70Lys), ExAC rs782407054, gnomAD rs782407054, REVEL 0.24, CADD 21.80, Uncertain significance
- T70M (p.Thr70Met), cosmic curated COSV10064, ExAC rs782407054, gnomAD rs782407054, REVEL 0.15, CADD 22.30, Uncertain significance, Inborn genetic diseases
- R71K (p.Arg71Lys), ExAC rs782163286, gnomAD rs782163286, REVEL 0.02, CADD 3.04
- D72A (p.Asp72Ala), rs2521036025, ClinGen CA415139394, ClinVar RCV002307849, Likely pathogenic, Muscular dystrophy, limb-girdle, autosomal recessive 23
- D72N (p.Asp72Asn), rs1557093462, gnomAD rs1557093462, REVEL 0.26, CADD 21.30, Variant assessed as somatic; moderate impact.
- G73C (p.Gly73Cys), Ensembl rs2148500138, REVEL 0.66, CADD 24.90
- P78L (p.Pro78Leu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- P78S (p.Pro78Ser), rs144542429, ClinGen CA10554627, ClinVar RCV000604142, ClinVar RCV001457196, REVEL 0.17, CADD 23.30, Conflicting interpretations, Spastic paraplegia; Inborn genetic diseases; not specified
- K79N (p.Lys79Asn), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62829, Variant assessed as somatic; moderate impact.
- E80Q (p.Glu80Gln), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62828, Variant assessed as somatic; moderate impact.
- L82M (p.Leu82Met), Ensembl rs2148500124
- G83D (p.Gly83Asp), gnomAD rs2064778370, REVEL 0.41, CADD 12.90, Uncertain significance, Spastic paraplegia
- G83R (p.Gly83Arg), rs2521035725, ClinGen CA415138860, ClinVar RCV003416709, Uncertain significance, L1CAM-related disorder
- G83S (p.Gly83Ser), rs2521035725, ClinGen CA415138864, ClinVar RCV003751731, Uncertain significance, Spastic paraplegia
- V84L (p.Val84Leu), rs2521035690, ClinGen CA415138822, ClinVar RCV002819227, Uncertain significance, Spastic paraplegia
- V86M (p.Val86Met), rs149309725, ClinGen CA245105, ClinVar RCV000178098, ClinVar RCV002453634, REVEL 0.25, CADD 16.60, Conflicting interpretations, not provided; Spastic paraplegia; Inborn genetic diseases
- Q88* (p.Gln88Ter), gnomAD rs1557093439
- S89* (p.Ser89Ter), rs782178366, ClinGen CA415138581, ClinVar RCV000493177, 1000Genomes rs782178366, AlphaMissense 0.25, MetaLR 0.28, Pathogenic
- S89L (p.Ser89Leu), rs782178366, ClinGen CA10554626, ClinVar RCV000864758, 1000Genomes rs782178366, REVEL 0.16, AlphaMissense 0.25, Benign, Spastic paraplegia
- P90L (p.Pro90Leu), rs782384760, ClinGen CA10554624, ClinVar RCV003750326, ExAC rs782384760, REVEL 0.23, CADD 20.60, Likely benign, Spastic paraplegia
- P90T (p.Pro90Thr), Ensembl rs2064778040, REVEL 0.18, CADD 11.70
- H91Q (p.His91Gln), ExAC rs782676482, gnomAD rs782676482, REVEL 0.13, CADD 10.40, Likely benign
- S92C (p.Ser92Cys), NCI-TCGA Cosmic COSV6283, Variant assessed as somatic; moderate impact.
- S92P (p.Ser92Pro), Ensembl rs2148500077
- G93A (p.Gly93Ala), Ensembl rs879950376
- T96I (p.Thr96Ile), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62828, Variant assessed as somatic; moderate impact.
- T96S (p.Thr96Ser), ESP rs369322647, ExAC rs369322647, TOPMed rs369322647, gnomAD rs369322647, REVEL 0.04, CADD 12.70
- I97V (p.Ile97Val), rs2521035312, ClinGen CA415138274, ClinVar RCV002760152, NCI-TCGA Cosmic COSV6282, Uncertain significance, Spastic paraplegia
- T98A (p.Thr98Ala), rs2148500068, ClinGen CA415138242, ClinVar RCV001844497, Ensembl rs2148500068, AlphaMissense 0.18, MetaLR 0.26, Uncertain significance, not specified
- T98M (p.Thr98Met), rs375000497, ClinGen CA10554619, ClinVar RCV003590809, ESP rs375000497, REVEL 0.22, CADD 15.00, Benign, Spastic paraplegia
- T98R (p.Thr98Arg), ESP rs375000497, ExAC rs375000497, TOPMed rs375000497, gnomAD rs375000497, REVEL 0.39, CADD 17.10, Likely benign, Spastic paraplegia
- G99C (p.Gly99Cys), ExAC rs781861107, gnomAD rs781861107
- G99D (p.Gly99Asp), Ensembl rs2064777599
- G99S (p.Gly99Ser), ExAC rs781861107, gnomAD rs781861107, REVEL 0.32, CADD 18.30
- N100K (p.Asn100Lys), Ensembl rs1239375900, REVEL 0.23, CADD 22.70
- N101Y (p.Asn101Tyr), TOPMed rs1459462593
- A105P (p.Ala105Pro), TOPMed rs1192196478, REVEL 0.11, CADD 17.30
- Q106H (p.Gln106His), ExAC rs782780120, TOPMed rs782780120, gnomAD rs782780120, REVEL 0.05, CADD 20.40, Likely benign, Spastic paraplegia
- Q106R (p.Gln106Arg), rs1557093395, ClinGen CA415138046, ClinVar RCV003751420, gnomAD rs1557093395, REVEL 0.06, CADD 19.70, Likely benign, Spastic paraplegia
- R107K (p.Arg107Lys), rs1267143652, NCI-TCGA Cosmic COSV6282, cosmic curated COSV62829, TOPMed rs1267143652, REVEL 0.04, CADD 16.30, Variant assessed as somatic; moderate impact.
- Q109H (p.Gln109His), ExAC rs782151953, gnomAD rs782151953, REVEL 0.24, CADD 24.00
- G110D (p.Gly110Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R113C (p.Arg113Cys), rs1434074663, ClinGen CA415137842, ClinVar RCV003752292, TOPMed rs1434074663, REVEL 0.26, CADD 28.20, Likely benign, Spastic paraplegia
- R113H (p.Arg113His), rs781908326, ClinGen CA10554614, NCI-TCGA Cosmic COSV6282, cosmic curated COSV62827, REVEL 0.21, CADD 24.60, Conflicting interpretations, History of neurodevelopmental disorder; Spastic paraplegia
- R113L (p.Arg113Leu), ExAC rs781908326, TOPMed rs781908326, gnomAD rs781908326, REVEL 0.18, CADD 23.30, Benign
- C114W (p.Cys114Trp), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- A116G (p.Ala116Gly), ExAC rs782704314, TOPMed rs782704314, gnomAD rs782704314, REVEL 0.48, CADD 25.80
- A116V (p.Ala116Val), ExAC rs782704314, TOPMed rs782704314, gnomAD rs782704314, REVEL 0.35, CADD 26.50
- S117C (p.Ser117Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K119E (p.Lys119Glu), NCI-TCGA TCGA novel, REVEL 0.10, CADD 10.70, Variant assessed as somatic; moderate impact.
- L120V (p.Leu120Val), rs796052697, UniProt VAR 078355, Benign
- G121S (p.Gly121Ser), UniProt VAR 003922, Pathogenic, in HYCX
- T122N (p.Thr122Asn), TOPMed rs1169318908
- A123S (p.Ala123Ser), ExAC rs782752037, TOPMed rs782752037, gnomAD rs782752037, REVEL 0.35, CADD 24.70, Likely benign
- A123T (p.Ala123Thr), rs782752037, ClinGen CA10554610, cosmic curated COSV62827, ClinVar RCV000867169, REVEL 0.36, CADD 25.40, Conflicting interpretations, Spastic paraplegia; not specified; not provided
- M124T (p.Met124Thr), gnomAD rs1557093368
- M124V (p.Met124Val), rs1366669213, ClinGen CA415137589, ClinVar RCV003590786, TOPMed rs1366669213, REVEL 0.10, CADD 15.30, Likely benign, Spastic paraplegia
- E127D (p.Glu127Asp), TOPMed rs1387074915, gnomAD rs1387074915, REVEL 0.07, CADD 20.50
- R129L (p.Arg129Leu), ExAC rs200809259, TOPMed rs200809259, gnomAD rs200809259, REVEL 0.18, CADD 14.70, Benign
- R129Q (p.Arg129Gln), rs200809259, ClinGen CA245107, ClinVar RCV000178099, ClinVar RCV001515064, REVEL 0.06, CADD 10.20, Conflicting interpretations, Spastic paraplegia; not provided
- R129W (p.Arg129Trp), rs201978087, ClinGen CA10554609, ClinVar RCV001532221, ClinVar RCV002359156, REVEL 0.20, CADD 23.90, Conflicting interpretations, Spastic paraplegia; not provided; MASA syndrome
- M131I (p.Met131Ile), rs782178903, ClinGen CA10554607, ClinVar RCV003590935, ExAC rs782178903, REVEL 0.21, CADD 12.70, Likely benign, Spastic paraplegia
- M131T (p.Met131Thr), Ensembl rs2064776688, REVEL 0.21, CADD 17.30
- M131V (p.Met131Val), rs782416322, ClinGen CA10554608, ClinVar RCV003088802, ClinVar RCV003434573, REVEL 0.15, CADD 10.90, Likely benign, Spastic paraplegia; not provided
- E133K (p.Glu133Lys), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62829, TOPMed rs1603276528, REVEL 0.50, CADD 23.90, Variant assessed as somatic; moderate impact.
- G134A (p.Gly134Ala), TOPMed rs1305263894, REVEL 0.17, CADD 22.90
- G134S (p.Gly134Ser), rs1557093353, ClinGen CA415137340, ClinVar RCV000519281, Ensembl rs1557093353, AlphaMissense 0.14, MetaLR 0.17, Uncertain significance, not specified
- A135Q (p.Ala135Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P136L (p.Pro136Leu), rs2521026806, ClinGen CA415137082, ClinVar RCV002283233, Uncertain significance, not provided
- K137Q (p.Lys137Gln), rs1358848849, ClinGen CA415137079, ClinVar RCV003750392, gnomAD rs1358848849, REVEL 0.20, CADD 22.20, Likely benign, Spastic paraplegia
- K137R (p.Lys137Arg), TOPMed rs2064766204, REVEL 0.23, CADD 24.10
- K137S (p.Lys137Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P139T (p.Pro139Thr), ExAC rs781977792, gnomAD rs781977792
- K140M (p.Lys140Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K140R (p.Lys140Arg), gnomAD rs1557093020, REVEL 0.60, CADD 31.00
- T142S (p.Thr142Ser), ExAC rs782375245, gnomAD rs782375245, REVEL 0.16, CADD 21.30
- V143L (p.Val143Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V143M (p.Val143Met), gnomAD rs1557093013, REVEL 0.24, CADD 23.70
- P145S (p.Pro145Ser), rs1043690256, ClinGen CA337263942, ClinVar RCV003590974, TOPMed rs1043690256, REVEL 0.39, CADD 23.40, Likely benign, Spastic paraplegia
- V146M (p.Val146Met), rs199796566, ClinGen CA10554587, ClinVar RCV002132104, ClinVar RCV003418383, REVEL 0.28, CADD 22.20, Conflicting interpretations, L1CAM-related disorder; Spastic paraplegia
- E147Q (p.Glu147Gln), Ensembl rs201210351
- E149* (p.Glu149Ter), Ensembl rs868924672
- E149K (p.Glu149Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G151A (p.Gly151Ala), rs1064796291, ClinGen CA415136716, ClinVar RCV000802209, Ensembl rs1064796291, AlphaMissense 0.95, MetaLR 0.83, Uncertain significance, Spastic paraplegia
- G151E (p.Gly151Glu), rs1064796291, ClinGen CA16621238, ClinVar RCV000481510, Ensembl rs1064796291, AlphaMissense 0.95, MetaLR 0.83, Uncertain significance, not provided
- G151V (p.Gly151Val), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- E152* (p.Glu152Ter), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; high impact.
- E152K (p.Glu152Lys), rs2521026280, ClinGen CA415136710, ClinVar RCV003043277, REVEL 0.18, CADD 18.70, Uncertain significance, Spastic paraplegia
- S153T (p.Ser153Thr), rs2148499026, ClinGen CA415136684, ClinVar RCV001767818, Ensembl rs2148499026, AlphaMissense 0.37, MetaLR 0.43, Uncertain significance, not provided
- V154A (p.Val154Ala), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62826, Variant assessed as somatic; moderate impact.
- V155I (p.Val155Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P157T (p.Pro157Thr), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62826, Variant assessed as somatic; moderate impact.
- C158Y (p.Cys158Tyr), rs1603276234, ClinGen CA415136571, ClinVar RCV000794906, Ensembl rs1603276234, AlphaMissense 1.00, MetaLR 0.88, Likely pathogenic, Spastic paraplegia
- P160S (p.Pro160Ser), TOPMed rs1557093000, gnomAD rs1557093000, REVEL 0.76, CADD 24.20
- P161L (p.Pro161Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P162A (p.Pro162Ala), rs2521026140, ClinGen CA415136497, ClinVar RCV003019453, Uncertain significance, Spastic paraplegia
- P162L (p.Pro162Leu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, TOPMed rs2064765578, REVEL 0.06, CADD 15.00, Variant assessed as somatic; moderate impact.
- P162S (p.Pro162Ser), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- S163G (p.Ser163Gly), rs1603276226, ClinGen CA415136462, ClinVar RCV000803125, TOPMed rs1603276226, AlphaMissense 0.18, MetaLR 0.09, Uncertain significance, Spastic paraplegia
- A164V (p.Ala164Val), NCI-TCGA Cosmic COSV6282, cosmic curated COSV62827, Uncertain significance, L1CAM-related disorder
- P166A (p.Pro166Ala), rs2064765468, ClinGen CA415136380, ClinVar RCV003590894, TOPMed rs2064765468, REVEL 0.29, CADD 22.70, Uncertain significance, Spastic paraplegia
- I169V (p.Ile169Val), gnomAD rs1557092993, REVEL 0.33, CADD 24.20
- M172I (p.Met172Ile), UniProt VAR 078358, Pathogenic, found in a patient with L1 syndrome
- K175Q (p.Lys175Gln), gnomAD rs202164138, REVEL 0.13, CADD 19.40
- I179S (p.Ile179Ser), rs137852523, ClinGen CA254961, ClinVar RCV000010676, UniProt VAR 003923, AlphaMissense 0.95, MetaLR 0.54, Pathogenic, MASA syndrome
- K180R (p.Lys180Arg), ExAC rs782537495, gnomAD rs782537495, REVEL 0.10, CADD 16.80
- D182E (p.Asp182Glu), NCI-TCGA TCGA novel, Uncertain significance, not provided
- E183K (p.Glu183Lys), rs782698098, ClinGen CA10554553, ClinVar RCV003870487, ExAC rs782698098, REVEL 0.33, CADD 20.20, Benign, Spastic paraplegia
- R184G (p.Arg184Gly), UniProt VAR 078359, Pathogenic, found in L1 syndrome
- R184Q (p.Arg184Gln), rs137852521, ClinGen CA254959, ClinVar RCV000010672, ClinVar RCV001824565, AlphaMissense 0.55, MetaLR 0.74, Pathogenic, Inborn genetic diseases; Spastic paraplegia; L1 syndrome
Public L1CAM analysis runs
- L1CAM analysis run — L1CAM (1,359 variants) — completed 2026-08-22