CLN3 (Battenin) variants and mutations
CLN3 (also known as Battenin) is a human protein-coding gene encoding a battenin protein. It participates in lysosomal and endosomal homeostasis, membrane trafficking, and cellular lipid handling, although its complete molecular role remains unresolved. Biallelic loss-of-function variants cause juvenile neuronal ceroid lipofuscinosis, with progressive vision loss, epilepsy, cognitive decline, and motor impairment. This analysis covers 844 CLN3 variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes neuronal ceroid lipofuscinosis 3, CLN3 disease, and neuronal ceroid lipofuscinosis. Example CLN3 variants include M1I, M1L, and M1T.
Variant analysis overview
- Gene: CLN3
- Protein: Battenin
- UniProt accession: Q13286
- Organism: Homo sapiens
- Variants analyzed: 844
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 671 unspecified-consequence records; 65 synonymous variants; 83 missense variants; 3 stop-gained variants; 15 frameshift variants; 2 in-frame deletions; 1 splice-region variants; 1 protein altering variant; 1 in-frame insertions; 2 substitution
- Prediction scores: 657 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neuronal ceroid lipofuscinosis 3, CLN3 disease, neuronal ceroid lipofuscinosis, juvenile neuronal ceroid lipofuscinosis, retinitis pigmentosa, Retinal dystrophy, hereditary disease, infantile neuronal ceroid lipofuscinosis, Cone rod dystrophy, cone-rod dystrophy, severe early-childhood-onset retinal dystrophy, inherited retinal dystrophy.
Protein structure and variant hotspots
- Protein features: 6 transmembrane segments; 6 post-translational modification sites.
- Structural context: 222 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, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable CLN3 variants
Examples include M1I, M1L, M1T, M1V, G2R, G3D, G3R, G3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2506530720, ClinGen CA395347587, ClinVar RCV003648137, Pathogenic/Likely pathogenic, Juvenile neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis
- M1L (p.Met1Leu), rs386833708, ClinGen CA263637, ClinVar RCV000049669, ClinVar RCV002513684, MetaLR 0.90, MetaSVM 0.99, Uncertain significance, Juvenile neuronal ceroid lipofuscinosis
- M1T (p.Met1Thr), rs777625354, ClinGen CA7981127, ClinVar RCV000409421, ClinVar RCV003333982, MetaLR 0.91, MetaSVM 0.95, Conflicting interpretations, not provided; Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis 3
- M1V (p.Met1Val), rs386833708, ClinGen CA7981128, ClinVar RCV000664968, ClinVar RCV001868197, MetaLR 0.90, MetaSVM 0.99, Pathogenic/Likely pathogenic, CLN3-related disorder; Neuronal ceroid lipofuscinosis
- G2R (p.Gly2Arg), TOPMed rs2046319139, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10011, CADD 23.20, PolyPhen-2 0.55, Variant assessed as somatic; moderate impact.
- G3D (p.Gly3Asp), rs756062000, ClinGen CA7981126, ClinVar RCV000463414, ClinVar RCV005614408, CADD 17.70, PolyPhen-2 0.04, Uncertain significance, Neuronal ceroid lipofuscinosis
- G3R (p.Gly3Arg), rs1398814860, ClinGen CA395347578, ClinVar RCV002001655, TOPMed rs1398814860, AlphaMissense 0.14, MetaLR 0.70, Uncertain significance, Neuronal ceroid lipofuscinosis
- G3S (p.Gly3Ser), rs1398814860, ClinGen CA395347579, ClinVar RCV001997578, TOPMed rs1398814860, AlphaMissense 0.14, MetaLR 0.70, Uncertain significance, Neuronal ceroid lipofuscinosis
- A5T (p.Ala5Thr), gnomAD rs1213007861, CADD 19.60, PolyPhen-2 0.33, Pathogenic/Likely pathogenic, Retinal dystrophy; Neuronal ceroid lipofuscinosis 3; Inborn genetic diseases
- A5V (p.Ala5Val), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10011, Ensembl rs2046318971, Variant assessed as somatic; moderate impact.
- S7R (p.Ser7Arg), rs2506530490, ClinGen CA2580091425, ClinVar RCV002815571, ClinVar RCV003465838, Pathogenic
- R8Q (p.Arg8Gln), rs2506530406, ClinGen CA395347546, ClinVar RCV003088803, CADD 20.90, PolyPhen-2 0.00, Uncertain significance, not specified; Neuronal ceroid lipofuscinosis
- R9W (p.Arg9Trp), NCI-TCGA Cosmic COSV6048, cosmic curated COSV60489, Variant assessed as somatic; moderate impact.
- R10H (p.Arg10His), rs2046318806, ClinGen CA395347535, ClinVar RCV002584016, CADD 22.70, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- R10L (p.Arg10Leu), TOPMed rs2046318806, gnomAD rs2046318806, CADD 23.00, PolyPhen-2 0.09
- F11S (p.Phe11Ser), rs752205710, ClinGen CA7981125, ClinVar RCV000479351, ClinVar RCV001345690, CADD 23.70, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis 3; Inborn genetic diseases; not provided
- S12L (p.Ser12Leu), cosmic curated COSV10011, gnomAD rs1218301566, CADD 20.20, PolyPhen-2 0.00
- D13N (p.Asp13Asn), ExAC rs754562266, TOPMed rs754562266, gnomAD rs754562266, CADD 23.10, PolyPhen-2 0.10, Uncertain significance
- D13Y (p.Asp13Tyr), rs754562266, ClinGen CA7981123, ClinVar RCV003058685, ExAC rs754562266, CADD 25.50, PolyPhen-2 0.22, Uncertain significance, Neuronal ceroid lipofuscinosis
- S14F (p.Ser14Phe), rs2141722690, ClinGen CA395347509, ClinVar RCV001896317, Ensembl rs2141722690, AlphaMissense 0.15, MetaLR 0.86, Uncertain significance, Neuronal ceroid lipofuscinosis
- S14Y (p.Ser14Tyr), cosmic curated COSV60488
- E15* (p.Glu15Ter), rs1228953213, ClinGen CA395347505, ClinVar RCV001384656, gnomAD rs1228953213, AlphaMissense 0.11, MetaLR 0.71, Pathogenic
- E15G (p.Glu15Gly), Ensembl rs1596568083
- E15K (p.Glu15Lys), rs1228953213, ClinGen CA395347507, ClinVar RCV003104688, gnomAD rs1228953213, AlphaMissense 0.11, MetaLR 0.71, Uncertain significance, Neuronal ceroid lipofuscinosis
- G16E (p.Gly16Glu), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10011, Uncertain significance, Neuronal ceroid lipofuscinosis
- E17* (p.Glu17Ter), rs386833726, ClinGen CA263691, cosmic curated COSV10011, ClinVar RCV000049688, CADD 38.00, Pathogenic
- E17K (p.Glu17Lys), rs386833726, ClinGen CA313732, cosmic curated COSV60491, ClinVar RCV000505765, CADD 24.00, PolyPhen-2 0.68, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofus
- E17V (p.Glu17Val), Ensembl rs2046314521, CADD 26.10, PolyPhen-2 0.72
- E18* (p.Glu18Ter), cosmic curated COSV10645
- E18D (p.Glu18Asp), rs2141722130, ClinGen CA395347162, ClinVar RCV002037983, Ensembl rs2141722130, CADD 9.93, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- E18G (p.Glu18Gly), rs2046314460, ClinGen CA395347164, ClinVar RCV001325663, Ensembl rs2046314460, AlphaMissense 0.08, MetaLR 0.76, Uncertain significance, Neuronal ceroid lipofuscinosis
- T19I (p.Thr19Ile), rs758020045, ClinGen CA7981087, cosmic curated COSV60492, ClinVar RCV002653547, CADD 15.80, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis; not provided
- T19S (p.Thr19Ser), ExAC rs758020045, TOPMed rs758020045, gnomAD rs758020045, Uncertain significance
- P21L (p.Pro21Leu), rs562525993, ClinGen CA7981085, ClinVar RCV001227479, 1000Genomes rs562525993, CADD 10.30, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- P21R (p.Pro21Arg), rs562525993, ClinGen CA7981086, ClinVar RCV002580284, 1000Genomes rs562525993, CADD 9.75, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis
- P23S (p.Pro23Ser), rs757558651, ClinGen CA7981084, ClinVar RCV000467562, ExAC rs757558651, CADD 8.81, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- R24Q (p.Arg24Gln), ExAC rs764455367, CADD 7.75, PolyPhen-2 0.00, Likely benign, Neuronal ceroid lipofuscinosis; Inborn genetic diseases
- R24W (p.Arg24Trp), TOPMed rs1383936390, gnomAD rs1383936390, CADD 23.20, PolyPhen-2 0.55, Uncertain significance, Inborn genetic diseases; not provided; not specified
- L25F (p.Leu25Phe), ExAC rs752737552, TOPMed rs752737552, gnomAD rs752737552, CADD 4.35, PolyPhen-2 0.12, Uncertain significance, Neuronal ceroid lipofuscinosis
- L25I (p.Leu25Ile), ExAC rs752737552, TOPMed rs752737552, gnomAD rs752737552, CADD 1.20, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis
- P26L (p.Pro26Leu), NCI-TCGA Cosmic COSV6049, cosmic curated COSV60491, Uncertain significance, not provided
- L27P (p.Leu27Pro), rs2506527055, ClinGen CA395347093, ClinVar RCV002671258, Uncertain significance, Neuronal ceroid lipofuscinosis
- L27V (p.Leu27Val), TOPMed rs2046313835, CADD 9.54, PolyPhen-2 0.04
- L28S (p.Leu28Ser), cosmic curated COSV60491, Ensembl rs1040287399
- D29E (p.Asp29Glu), rs1131691496, ClinGen CA395347058, ClinVar RCV000493571, ClinVar RCV002298623, CADD 15.50, PolyPhen-2 0.00, Uncertain significance, not provided; Neuronal ceroid lipofuscinosis
- D29N (p.Asp29Asn), gnomAD rs1211763551, CADD 16.20, PolyPhen-2 0.03, Uncertain significance, not provided
- H30R (p.His30Arg), rs1399199073, ClinGen CA395347037, ClinVar RCV000546992, TOPMed rs1399199073, CADD 0.25, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- Q31R (p.Gln31Arg), TOPMed rs1331250366, gnomAD rs1331250366, CADD 0.26, PolyPhen-2 0.00
- A33G (p.Ala33Gly), gnomAD rs1227931688, CADD 16.90, PolyPhen-2 0.00
- A33S (p.Ala33Ser), cosmic curated COSV60495
- A33T (p.Ala33Thr), TOPMed rs1268855278, gnomAD rs1268855278
- A33V (p.Ala33Val), gnomAD rs1227931688, CADD 11.90, PolyPhen-2 0.00
- H34L (p.His34Leu), rs759668300, ClinGen CA7981078, ClinVar RCV003027713, ExAC rs759668300, CADD 10.30, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- H34R (p.His34Arg), rs759668300, ClinGen CA7981079, ClinVar RCV001050603, ClinVar RCV004973302, CADD 8.90, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- H34Y (p.His34Tyr), TOPMed rs1245582061, gnomAD rs1245582061, CADD 7.47
- W35* (p.Trp35Ter), rs386833700, ClinGen CA263613, ClinVar RCV000049661, ClinVar RCV000760369, CADD 38.00, Pathogenic
- W35S (p.Trp35Ser), cosmic curated COSV60493
- N37K (p.Asn37Lys), rs776507846, ClinGen CA395346903, cosmic curated COSV60494, ClinVar RCV002851207, AlphaMissense 0.84, MetaLR 0.89, Uncertain significance, Neuronal ceroid lipofuscinosis
- A38T (p.Ala38Thr), 1000Genomes rs565082957, ExAC rs565082957, gnomAD rs565082957, CADD 19.30
- V39A (p.Val39Ala), ExAC rs760656860, TOPMed rs760656860, gnomAD rs760656860, CADD 18.30, PolyPhen-2 0.00
- V39M (p.Val39Met), TOPMed rs1201013104
- F41I (p.Phe41Ile), cosmic curated COSV10465
- W42* (p.Trp42Ter), rs781617143, ClinGen CA7981045, ClinVar RCV002644413, ClinVar RCV003465993, CADD 38.00, Pathogenic
- G45C (p.Gly45Cys), gnomAD rs1431357492
- L46I (p.Leu46Ile), gnomAD rs1360860411
- L46V (p.Leu46Val), rs1360860411, ClinGen CA395346566, ClinVar RCV003026801, AlphaMissense 0.32, MetaLR 0.97, Uncertain significance, Neuronal ceroid lipofuscinosis
- N48I (p.Asn48Ile), rs2506508693, ClinGen CA395346548, ClinVar RCV003036446, Uncertain significance, Neuronal ceroid lipofuscinosis
- N48S (p.Asn48Ser), rs2506508693, ClinGen CA395346550, ClinVar RCV002658284, Uncertain significance, Neuronal ceroid lipofuscinosis
- N49H (p.Asn49His), rs2506508655, ClinGen CA395346545, ClinVar RCV002797263, CADD 26.90, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- N49K (p.Asn49Lys), rs571216643, ClinGen CA395346538, ClinVar RCV001526712, ClinVar RCV001873711, CADD 23.40, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis 3; Neuronal ceroid lipofuscinosis
- N49S (p.Asn49Ser), rs1474384057, ClinGen CA395346540, ClinVar RCV001926761, TOPMed rs1474384057, CADD 25.30, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- S51F (p.Ser51Phe), rs780151271, ClinGen CA7981042, ClinVar RCV000594773, ClinVar RCV000765284, CADD 27.90, PolyPhen-2 0.99, Uncertain significance, not provided; Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis 3
- Y52C (p.Tyr52Cys), gnomAD rs1433328820
- V53A (p.Val53Ala), Ensembl rs1160156723
- V53M (p.Val53Met), ExAC rs750643595, gnomAD rs750643595, CADD 25.60, PolyPhen-2 1.00
- V54M (p.Val54Met), TOPMed rs2046275516
- M55I (p.Met55Ile), TOPMed rs1173668936
- M55L (p.Met55Leu), ExAC rs760481173, TOPMed rs760481173, gnomAD rs760481173, Uncertain significance, Juvenile neuronal ceroid lipofuscinosis
- M55V (p.Met55Val), ExAC rs760481173, TOPMed rs760481173, gnomAD rs760481173
- L56M (p.Leu56Met), ExAC rs767513559, gnomAD rs767513559, CADD 24.90, PolyPhen-2 1.00
- L56V (p.Leu56Val), ExAC rs767513559, gnomAD rs767513559, CADD 24.90, PolyPhen-2 1.00
- S57G (p.Ser57Gly), TOPMed rs951644149, gnomAD rs951644149, CADD 27.00, PolyPhen-2 1.00
- S57N (p.Ser57Asn), rs2506508333, ClinGen CA395346492, ClinVar RCV002952658, Uncertain significance, Neuronal ceroid lipofuscinosis
- A58V (p.Ala58Val), cosmic curated COSV10034, CADD 25.60, PolyPhen-2 1.00
- A59T (p.Ala59Thr), rs765893479, ClinGen CA7981034, ClinVar RCV001222663, ClinVar RCV001810499, CADD 24.90, PolyPhen-2 1.00, Pathogenic/Likely pathogenic, Retinal dystrophy; Neuronal ceroid lipofuscinosis 3; Inborn genetic diseases
- D61N (p.Asp61Asn), rs772851701, ClinGen CA7981032, cosmic curated COSV61107, ClinVar RCV001952199, CADD 25.80, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- I62V (p.Ile62Val), TOPMed rs1567262947, CADD 24.00, PolyPhen-2 0.94
- L63F (p.Leu63Phe), cosmic curated COSV10465, CADD 17.70
- S64N (p.Ser64Asn), rs2046274351, ClinGen CA395346446, ClinVar RCV001245596, Ensembl rs2046274351, AlphaMissense 0.12, MetaLR 0.82, Uncertain significance, Neuronal ceroid lipofuscinosis
- H65R (p.His65Arg), gnomAD rs574261896, CADD 17.00, PolyPhen-2 0.08
- K66E (p.Lys66Glu), rs963189449, ClinGen CA279786566, cosmic curated COSV99048, ClinVar RCV001315650, AlphaMissense 0.06, MetaLR 0.47, Uncertain significance, Neuronal ceroid lipofuscinosis
- K66Q (p.Lys66Gln), rs963189449, ClinGen CA395346434, ClinVar RCV002861357, AlphaMissense 0.06, MetaLR 0.47, Uncertain significance, Neuronal ceroid lipofuscinosis
- K66R (p.Lys66Arg), rs769447444, ClinGen CA7981031, cosmic curated COSV10736, ClinVar RCV002047051, CADD 18.50, PolyPhen-2 0.08, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- T68A (p.Thr68Ala), NCI-TCGA Cosmic COSV6110, cosmic curated COSV61105, Variant assessed as somatic; moderate impact.
- S69L (p.Ser69Leu), rs769840061, ClinGen CA313767, cosmic curated COSV10034, ClinVar RCV000187025, CADD 21.40, PolyPhen-2 0.24, Uncertain significance, not provided; Inborn genetic diseases; not specified
- S69P (p.Ser69Pro), ExAC rs748458737, TOPMed rs748458737, gnomAD rs748458737
- S69T (p.Ser69Thr), ExAC rs748458737, TOPMed rs748458737, gnomAD rs748458737, CADD 1.94
- S69W (p.Ser69Trp), rs769840061, ClinGen CA395346412, ClinVar RCV001116112, ClinVar RCV001363020, CADD 25.40, PolyPhen-2 0.96, Uncertain significance, Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis 3
- G70E (p.Gly70Glu), rs747526330, ClinGen CA7981028, NCI-TCGA Cosmic COSV6110, cosmic curated COSV61104, CADD 13.10, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis
- N71S (p.Asn71Ser), TOPMed rs2046273627
- Q72* (p.Gln72Ter), rs386833709, ClinGen CA263642, ClinVar RCV000049670, ClinVar RCV000812617, CADD 36.00, Pathogenic
- Q72H (p.Gln72His), ExAC rs758501983, TOPMed rs758501983, gnomAD rs758501983, CADD 13.30, PolyPhen-2 0.01, Uncertain significance, not provided
- Q72L (p.Gln72Leu), ExAC rs780482162, gnomAD rs780482162, CADD 20.80, PolyPhen-2 0.23
- S73N (p.Ser73Asn), rs2046273337, ClinGen CA395346390, ClinVar RCV003531420, TOPMed rs2046273337, CADD 22.20, PolyPhen-2 0.91, Uncertain significance, Neuronal ceroid lipofuscinosis
- H74R (p.His74Arg), TOPMed rs1180074704, gnomAD rs1180074704, CADD 23.60, PolyPhen-2 0.77
- H74Y (p.His74Tyr), ExAC rs745941670, gnomAD rs745941670, CADD 26.80, PolyPhen-2 0.90
- G78D (p.Gly78Asp), ExAC rs768993577, TOPMed rs768993577, gnomAD rs768993577, CADD 1.33, PolyPhen-2 0.00
- P79L (p.Pro79Leu), rs1596564333, ClinGen CA395346327, ClinVar RCV000793950, Ensembl rs1596564333, AlphaMissense 0.07, MetaLR 0.20, Uncertain significance, Neuronal ceroid lipofuscinosis
- P79S (p.Pro79Ser), gnomAD rs2046263535, CADD 22.50, PolyPhen-2 0.82
- T80A (p.Thr80Ala), 1000Genomes rs150348015, ESP rs150348015, ExAC rs150348015, TOPMed rs150348015, CADD 1.58, PolyPhen-2 0.01, Uncertain significance, Neuronal ceroid lipofuscinosis
- T80K (p.Thr80Lys), ExAC rs775999656, TOPMed rs775999656, gnomAD rs775999656, Uncertain significance
- T80M (p.Thr80Met), rs775999656, ClinGen CA7981008, cosmic curated COSV61105, ClinVar RCV000521226, CADD 13.70, PolyPhen-2 0.60, Uncertain significance, Neuronal ceroid lipofuscinosis; not provided; Neuronal ceroid lipofuscinosis 3
- T80S (p.Thr80Ser), rs150348015, ClinGen CA7981009, ClinVar RCV000632734, ClinVar RCV001721545, CADD 0.51, PolyPhen-2 0.02, Conflicting interpretations, Inborn genetic diseases; not provided; Neuronal ceroid lipofuscinosis 3
- P81L (p.Pro81Leu), rs137906617, ClinGen CA313772, ClinVar RCV000725785, ClinVar RCV000791120, CADD 18.00, PolyPhen-2 0.57, Conflicting interpretations, Inborn genetic diseases; not provided; Neuronal ceroid lipofuscinosis
- I82F (p.Ile82Phe), ESP rs370020452, ExAC rs370020452, TOPMed rs370020452, gnomAD rs370020452, CADD 6.74, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- I82M (p.Ile82Met), gnomAD rs1344708788
- P83L (p.Pro83Leu), rs749503213, ClinGen CA7981004, cosmic curated COSV10647, ClinVar RCV002761108, CADD 19.80, PolyPhen-2 0.17, Uncertain significance, Neuronal ceroid lipofuscinosis
- P83S (p.Pro83Ser), cosmic curated COSV10465, Uncertain significance, Neuronal ceroid lipofuscinosis; not specified; not provided
- H84N (p.His84Asn), 1000Genomes rs201329358, ExAC rs201329358, TOPMed rs201329358, gnomAD rs201329358, CADD 13.80, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases; not provided; Neuronal ceroid lipofuscinosis
- H84R (p.His84Arg), rs2046262515, ClinGen CA395346290, ClinVar RCV001047365, Ensembl rs2046262515, CADD 15.10, PolyPhen-2 0.20, Uncertain significance, Neuronal ceroid lipofuscinosis
- H84Y (p.His84Tyr), 1000Genomes rs201329358, ExAC rs201329358, TOPMed rs201329358, gnomAD rs201329358, CADD 9.74, PolyPhen-2 0.01, Uncertain significance
- N85D (p.Asn85Asp), TOPMed rs996285915, gnomAD rs996285915, Uncertain significance
- N85H (p.Asn85His), TOPMed rs996285915, gnomAD rs996285915, CADD 24.50, PolyPhen-2 0.98, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- S87L (p.Ser87Leu), rs2141717001, ClinGen CA395346264, ClinVar RCV001983317, Ensembl rs2141717001, AlphaMissense 0.15, MetaLR 0.90, Uncertain significance, Neuronal ceroid lipofuscinosis
- S88A (p.Ser88Ala), ExAC rs754801166, gnomAD rs754801166, CADD 24.20, PolyPhen-2 0.99
- S88T (p.Ser88Thr), ExAC rs754801166, gnomAD rs754801166, CADD 23.20, PolyPhen-2 1.00
- R89* (p.Arg89Ter), Ensembl rs386833713, CADD 38.00, Pathogenic
- R89L (p.Arg89Leu), rs766287694, ClinGen CA395346250, ClinVar RCV001053324, ExAC rs766287694, CADD 24.60, PolyPhen-2 0.99, Uncertain significance, Neuronal ceroid lipofuscinosis
- R89Q (p.Arg89Gln), rs766287694, ClinGen CA313778, ClinVar RCV000187027, ClinVar RCV000801221, CADD 24.10, PolyPhen-2 0.81, Uncertain significance, not provided; Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis 3
- F90L (p.Phe90Leu), rs145520962, ClinGen CA245999, cosmic curated COSV61108, ClinVar RCV000178825, CADD 22.10, PolyPhen-2 0.11, Uncertain significance, Inborn genetic diseases; not provided; Neuronal ceroid lipofuscinosis
- D91G (p.Asp91Gly), gnomAD rs1241022940, CADD 27.10, PolyPhen-2 1.00
- C92* (p.Cys92Ter), rs1443772167, ClinGen CA395346224, ClinVar RCV002308399, AlphaMissense 0.95, MetaLR 0.95, Likely pathogenic
- C92W (p.Cys92Trp), rs1443772167, ClinGen CA395346223, ClinVar RCV002577577, gnomAD rs1443772167, AlphaMissense 0.95, MetaLR 0.95, Uncertain significance, Neuronal ceroid lipofuscinosis
- N93D (p.Asn93Asp), ExAC rs761369095, TOPMed rs761369095, gnomAD rs761369095, CADD 27.00, PolyPhen-2 0.98, Uncertain significance, not provided; Neuronal ceroid lipofuscinosis
- N93H (p.Asn93His), ExAC rs761369095, TOPMed rs761369095, gnomAD rs761369095, CADD 24.60, PolyPhen-2 0.77, Uncertain significance
- N93S (p.Asn93Ser), rs140409296, ClinGen CA7981000, ClinVar RCV001060110, ClinVar RCV002436637, CADD 25.40, PolyPhen-2 0.98, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- S94C (p.Ser94Cys), TOPMed rs1471839976
- S94P (p.Ser94Pro), Ensembl rs1033393002, Uncertain significance, Inborn genetic diseases
- S94Y (p.Ser94Tyr), cosmic curated COSV10034
- V95I (p.Val95Ile), ExAC rs763659524, TOPMed rs763659524, CADD 16.40, PolyPhen-2 0.02, Uncertain significance, Neuronal ceroid lipofuscinosis
- V95L (p.Val95Leu), ExAC rs763659524, TOPMed rs763659524, CADD 17.10, PolyPhen-2 0.02, Uncertain significance
- S96A (p.Ser96Ala), gnomAD rs1344068672, CADD 25.30
- S96C (p.Ser96Cys), TOPMed rs2046260961
- T97M (p.Thr97Met), rs376421578, ClinGen CA7980998, cosmic curated COSV61106, ClinVar RCV000502862, CADD 33.00, PolyPhen-2 1.00, Uncertain significance, Inborn genetic diseases; not provided; not specified
- A98D (p.Ala98Asp), rs1361279384, ClinGen CA395346180, ClinVar RCV001342290, gnomAD rs1361279384, AlphaMissense 0.96, MetaLR 0.89, Uncertain significance, Neuronal ceroid lipofuscinosis
- A98V (p.Ala98Val), rs1361279384, ClinGen CA395346178, ClinVar RCV002904308, gnomAD rs1361279384, AlphaMissense 0.96, MetaLR 0.89, Uncertain significance, Neuronal ceroid lipofuscinosis
- A99P (p.Ala99Pro), TOPMed rs2046246370
- V100L (p.Val100Leu), rs1478662819, ClinGen CA395346156, ClinVar RCV000813000, ClinVar RCV005614450, CADD 24.70, Uncertain significance, Neuronal ceroid lipofuscinosis
- L101P (p.Leu101Pro), rs386833714, ClinGen CA263656, ClinVar RCV000049675, UniProt VAR 005131, CADD 29.10, PolyPhen-2 1.00, Likely pathogenic, Neuronal ceroid lipofuscinosis 3
- L102V (p.Leu102Val), rs1167562278, ClinGen CA395346145, ClinVar RCV001248304, TOPMed rs1167562278, AlphaMissense 0.42, MetaLR 0.94, Uncertain significance, Neuronal ceroid lipofuscinosis
- A103T (p.Ala103Thr), rs1462511334, ClinGen CA395346140, cosmic curated COSV61105, ClinVar RCV002829748, CADD 25.70, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- A103V (p.Ala103Val), rs760039703, ClinGen CA7980975, ClinVar RCV000480048, ClinVar RCV001047670, CADD 27.70, PolyPhen-2 1.00, Uncertain significance, not provided; Neuronal ceroid lipofuscinosis; Neuronal ceroid lipofuscinosis 3
- D104N (p.Asp104Asn), gnomAD rs1474018125
- I105F (p.Ile105Phe), rs11552531, ClinGen CA395346128, ClinVar RCV003002026, 1000Genomes rs11552531, CADD 26.60, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- I105V (p.Ile105Val), rs11552531, ClinGen CA288730, cosmic curated COSV10966, ClinVar RCV000116750, CADD 23.70, PolyPhen-2 1.00, Benign/Likely benign, Inborn genetic diseases; not specified; Neuronal ceroid lipofuscinosis
- L106H (p.Leu106His), rs2046245840, ClinGen CA395346119, cosmic curated COSV10606, ClinVar RCV001376527, AlphaMissense 0.95, MetaLR 0.95, Uncertain significance, Neuronal ceroid lipofuscinosis 3
- P107L (p.Pro107Leu), rs1231056238, ClinGen CA395346113, ClinVar RCV001236359, gnomAD rs1231056238, AlphaMissense 0.92, MetaLR 0.97, Uncertain significance, Neuronal ceroid lipofuscinosis
- P107R (p.Pro107Arg), rs1231056238, ClinGen CA395346114, ClinVar RCV003045484, AlphaMissense 0.92, MetaLR 0.97, Uncertain significance, Neuronal ceroid lipofuscinosis
- P107S (p.Pro107Ser), rs149095062, ClinGen CA7980973, cosmic curated COSV10465, ClinVar RCV000500791, CADD 24.90, PolyPhen-2 1.00, Uncertain significance, Neuronal ceroid lipofuscinosis; not specified; not provided
- T108A (p.Thr108Ala), rs1302804526, ClinGen CA395346110, ClinVar RCV001948408, TOPMed rs1302804526, CADD 22.90, PolyPhen-2 0.96, Uncertain significance, Neuronal ceroid lipofuscinosis
- T108I (p.Thr108Ile), rs769953653, ClinGen CA7980972, cosmic curated COSV10736, ClinVar RCV002907492, CADD 24.90, PolyPhen-2 1.00, Uncertain significance, Inborn genetic diseases; Neuronal ceroid lipofuscinosis
- T108S (p.Thr108Ser), rs1302804526, TOPMed rs1302804526, gnomAD rs1302804526, CADD 22.30, PolyPhen-2 0.78, Uncertain significance
- L109P (p.Leu109Pro), rs1232460841, ClinGen CA395346102, ClinVar RCV003048516, TOPMed rs1232460841, CADD 25.70, Uncertain significance, Neuronal ceroid lipofuscinosis
- V110I (p.Val110Ile), rs781534624, ClinGen CA7980970, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10034, CADD 0.00, PolyPhen-2 0.00, Uncertain significance, Neuronal ceroid lipofuscinosis
- I111V (p.Ile111Val), rs1331033517, ClinGen CA395346094, ClinVar RCV001296513, TOPMed rs1331033517, CADD 22.60, Uncertain significance, Neuronal ceroid lipofuscinosis
- K112R (p.Lys112Arg), ExAC rs771758062, gnomAD rs771758062, CADD 25.60, PolyPhen-2 1.00
- L113F (p.Leu113Phe), 1000Genomes rs200356262, ExAC rs200356262, TOPMed rs200356262, gnomAD rs200356262, Likely benign
- L113M (p.Leu113Met), cosmic curated COSV61105
- L113S (p.Leu113Ser), ExAC rs778765250, gnomAD rs778765250
- L113W (p.Leu113Trp), ExAC rs778765250, gnomAD rs778765250, CADD 24.90, PolyPhen-2 0.86
- A115V (p.Ala115Val), TOPMed rs1269378570, gnomAD rs1269378570, CADD 26.70, PolyPhen-2 0.99
- P116S (p.Pro116Ser), cosmic curated COSV61106
- L117F (p.Leu117Phe), Ensembl rs2141715063, CADD 13.50, PolyPhen-2 0.01
- L117I (p.Leu117Ile), cosmic curated COSV10465
- G118D (p.Gly118Asp), rs753305901, ClinGen CA7980965, ClinVar RCV001241267, ExAC rs753305901, CADD 23.40, PolyPhen-2 0.96, Uncertain significance, Neuronal ceroid lipofuscinosis
- L119A (p.Leu119Ala), rs2506494373, ClinGen CA2580091414, ClinVar RCV003136476, Pathogenic
- L119F (p.Leu119Phe), gnomAD rs1442290418, CADD 27.50, PolyPhen-2 0.98
- L119H (p.Leu119His), cosmic curated COSV10885, Ensembl rs2141715043
- H120N (p.His120Asn), rs145749864, ClinGen CA7980964, cosmic curated COSV61107, ClinVar RCV001874953, AlphaMissense 0.31, MetaLR 0.94, Uncertain significance, Neuronal ceroid lipofuscinosis
- H120Q (p.His120Gln), rs2046244666, ClinGen CA395346035, ClinVar RCV003271844, Ensembl rs2046244666, CADD 19.10, PolyPhen-2 0.87, Uncertain significance, Inborn genetic diseases
Public CLN3 analysis runs
- CLN3 analysis run — CLN3 (844 variants) — completed 2026-08-21