PLP1 (Myelin proteolipid protein) variants and mutations
PLP1 (also known as Myelin proteolipid protein) is a human protein-coding gene encoding a myelin proteolipid protein. It supports central-nervous-system myelin structure and is required for oligodendrocyte and axonal integrity. Gene duplication most commonly causes Pelizaeus-Merzbacher disease, while other variants can cause spastic paraplegia type 2 or milder leukodystrophy. This analysis covers 564 PLP1 variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes Pelizeaus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, and Spastic paraplegia type 2. Example PLP1 variants include M1?, M1I, and M1K.
Variant analysis overview
- Gene: PLP1
- Protein: Myelin proteolipid protein
- UniProt accession: P60201
- Organism: Homo sapiens
- Variants analyzed: 564
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 395 unspecified-consequence records; 103 synonymous variants; 2 frameshift variants; 56 missense variants; 1 stop-gained variants; 3 splice-region variants; 2 in-frame insertions; 4 substitution
- Prediction scores: 358 variants have prediction scores (63% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Pelizeaus-Merzbacher spectrum disorder, hereditary spastic paraplegia 2, Spastic paraplegia type 2, Sudanophilic leukodystrophy, Pelizaeus-Merzbacher disease, connatal form, hereditary disease, hereditary spastic paraplegia, null syndrome, Spastic paraplegia, Pelizaeus-Merzbacher disease, classic form, Pelizaeus-Merzbacher disease, transitional form, Pelizaeus-Merzbacher disease in female carriers.
Protein structure and variant hotspots
- Protein features: 4 transmembrane segments; 3 post-translational modification sites.
- Structural context: 215 variants have structural context.
- PTM context: 9 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 PLP1 variants
Examples include M1?, M1I, M1K, M1R, M1T, M1V, G2D, G2R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV58279
- M1I (p.Met1Ile), rs132630290, ClinGen CA121352, ClinVar RCV000011836, ClinVar RCV001851799, MetaLR 0.93, MetaSVM 0.93, Pathogenic
- M1K (p.Met1Lys), rs864622194, ClinVar RCV004595765, MetaLR 0.91, MetaSVM 0.96, Pathogenic, Pelizaeus-Merzbacher disease
- M1R (p.Met1Arg), rs864622194, ClinGen CA414101585, ClinVar RCV000624524, ClinVar RCV001805225, MetaLR 0.91, MetaSVM 0.96, Pathogenic, Inborn genetic diseases; Pelizaeus-Merzbacher disease; Hereditary spastic parapl
- M1T (p.Met1Thr), rs864622194, ClinGen CA348083, ClinVar RCV000203805, ClinVar RCV002517370, MetaLR 0.91, MetaSVM 0.96, Pathogenic, Inborn genetic diseases; Hereditary spastic paraplegia 2
- M1V (p.Met1Val), rs797045064, ClinGen CA276159, ClinVar RCV000191119, ClinVar RCV001857679, MetaLR 0.93, MetaSVM 0.91, Pathogenic, Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2
- G2D (p.Gly2Asp), rs2522300700, ClinGen CA414101722, ClinVar RCV003621801, NCI-TCGA TCGA novel, CADD 32.00, PolyPhen-2 1.00, Uncertain significance, Hereditary spastic paraplegia 2
- G2R (p.Gly2Arg), rs2522269017, ClinGen CA414101589, ClinVar RCV003314812, Uncertain significance, not provided
- L3L (p.Leu3Leu), rs765784563, gnomAD X-103785586-G-A, CADD 9.13
- E5* (p.Glu5Ter), cosmic curated COSV58277
- E5V (p.Glu5Val), gnomAD X-103785588-TAG-T, CADD 29.30
- E5E (p.Glu5Glu), rs753140839, gnomAD X-103785592-G-A, CADD 9.01
- C6G (p.Cys6Gly), ExAC rs763376651, gnomAD rs763376651, CADD 23.70, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases
- C6C (p.Cys6Cys), rs151116667, gnomAD X-103785595-C-T, CADD 11.70
- C7* (p.Cys7Ter), rs1038021317, ClinGen CA414101786, ClinVar RCV001329970, Ensembl rs1038021317, Pathogenic
- C7Y (p.Cys7Tyr), gnomAD X-103785597-G-A, CADD 27.40, PolyPhen-2 1.00
- A8G (p.Ala8Gly), Ensembl rs2074488457, CADD 24.80, PolyPhen-2 0.50
- R9* (p.Arg9Ter), rs2074488502, ClinGen CA414101799, ClinVar RCV001260516, Ensembl rs2074488502, Likely pathogenic
- R9G (p.Arg9Gly), gnomAD X-103785602-A-G, CADD 25.20, PolyPhen-2 0.56
- R9T (p.Arg9Thr), gnomAD X-103785603-G-C, CADD 24.80, PolyPhen-2 0.56
- C10Y (p.Cys10Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L11M (p.Leu11Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V12A (p.Val12Ala), rs1049312344, ClinGen CA334001106, ClinVar RCV000699424, TOPMed rs1049312344, CADD 20.20, PolyPhen-2 0.04, Uncertain significance, Hereditary spastic paraplegia 2
- V12L (p.Val12Leu), ExAC rs750073011, gnomAD rs750073011, CADD 21.60, PolyPhen-2 0.01
- V12I (p.Val12Ile), gnomAD X-103785611-G-A, CADD 20.20, PolyPhen-2 0.00
- G13R (p.Gly13Arg), ExAC rs755645540, gnomAD rs755645540, CADD 26.40, PolyPhen-2 1.00
- G13V (p.Gly13Val), cosmic curated COSV58277
- G13E (p.Gly13Glu), gnomAD X-103785615-G-A, CADD 25.80, PolyPhen-2 1.00
- A14D (p.Ala14Asp), rs1569427243, ClinGen CA414101853, ClinVar RCV000680073, Ensembl rs1569427243, AlphaMissense 0.97, MetaLR 0.93, Uncertain significance, Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2
- A14A (p.Ala14Ala), rs1408934381, gnomAD X-103785619-C-T, CADD 12.50
- P15L (p.Pro15Leu), rs11543022, ClinGen CA255678, ClinVar RCV000011824, ClinVar RCV001851798, AlphaMissense 0.98, MetaLR 0.98, Pathogenic/Likely pathogenic, not provided; Hereditary spastic paraplegia 2; Pelizaeus-Merzbacher disease
- P15S (p.Pro15Ser), rs11543017, ClinGen CA414101863, ClinVar RCV002861884, Uncertain significance, Hereditary spastic paraplegia 2
- P15P (p.Pro15Pro), rs2074488844, gnomAD X-103785622-C-A, CADD 10.30
- F16F (p.Phe16Phe), rs779620495, gnomAD X-103785625-T-C, CADD 13.40
- A17P (p.Ala17Pro), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10039, Variant assessed as somatic; moderate impact.
- A17T (p.Ala17Thr), rs797045890, ClinGen CA205100, ClinVar RCV000192345, ClinVar RCV001197987, CADD 25.70, PolyPhen-2 1.00, Uncertain significance, not specified; not provided; Pelizaeus-Merzbacher disease
- S18F (p.Ser18Phe), cosmic curated COSV10515
- L19P (p.Leu19Pro), rs2522301062, ClinVar RCV004595785, Likely pathogenic, Pelizaeus-Merzbacher disease
- L19V (p.Leu19Val), gnomAD X-103785632-C-G, CADD 17.40, PolyPhen-2 0.03
- L19L (p.Leu19Leu), gnomAD X-103785634-G-T, CADD 9.97
- A21V (p.Ala21Val), NCI-TCGA TCGA novel, Likely pathogenic, not provided
- A21A (p.Ala21Ala), rs753285570, gnomAD X-103785640-C-T, CADD 12.80
- T22A (p.Thr22Ala), TOPMed rs937672540, gnomAD rs937672540, AlphaMissense 0.79, MetaLR 0.97, Uncertain significance, Inborn genetic diseases
- T22P (p.Thr22Pro), rs937672540, ClinGen CA414101931, ClinVar RCV002214546, TOPMed rs937672540, AlphaMissense 0.79, MetaLR 0.97, Uncertain significance, not provided
- C25F (p.Cys25Phe), rs2147762985, ClinGen CA414101961, ClinVar RCV002255778, Ensembl rs2147762985, AlphaMissense 0.91, MetaLR 0.97, Uncertain significance, Pelizaeus-Merzbacher disease
- C25Y (p.Cys25Tyr), gnomAD X-103785651-G-A, CADD 25.90, PolyPhen-2 0.74
- F26L (p.Phe26Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G28E (p.Gly28Glu), rs2522301179, ClinGen CA414101999, ClinVar RCV003894079, ClinVar RCV004595714, Likely pathogenic, Pelizaeus-Merzbacher disease
- G28G (p.Gly28Gly), rs1057082923, gnomAD X-103785661-G-A, CADD 7.89
- V29L (p.Val29Leu), rs1376158201, ClinGen CA414102007, cosmic curated COSV58275, ClinVar RCV001207367, CADD 23.00, PolyPhen-2 0.21, Uncertain significance, not provided; Inborn genetic diseases; Hereditary spastic paraplegia 2
- V29V (p.Val29Val), rs754929570, gnomAD X-103785664-G-T, CADD 9.14
- A30P (p.Ala30Pro), UniProt VAR 070667, Pathogenic, in SPG2
- A30S (p.Ala30Ser), cosmic curated COSV58276
- A30T (p.Ala30Thr), gnomAD rs1372739626, CADD 26.10, PolyPhen-2 1.00
- A30V (p.Ala30Val), gnomAD X-103785666-C-T, CADD 25.30, PolyPhen-2 0.99
- A30A (p.Ala30Ala), rs2074489211, gnomAD X-103785667-A-G, CADD 11.30
- L31P (p.Leu31Pro), UniProt VAR 015014, Likely pathogenic, Pelizaeus-Merzbacher disease
- L31Q (p.Leu31Gln), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10039, Variant assessed as somatic; moderate impact., in HLD1
- L31R (p.Leu31Arg), rs2522301288, ClinVar RCV004595807, Likely pathogenic, Pelizaeus-Merzbacher disease
- L31V (p.Leu31Val), rs1391989749, ClinGen CA414102027, ClinVar RCV003238608, ClinVar RCV005432792, AlphaMissense 0.36, MetaLR 0.98, Uncertain significance, not specified; not provided
- L31L (p.Leu31Leu), rs1391989749, gnomAD X-103785668-C-T, AlphaMissense 0.36, MetaLR 0.98
- F32L (p.Phe32Leu), rs2522301325, ClinVar RCV004595809, UniProt VAR 015015, Likely pathogenic, Pelizaeus-Merzbacher disease
- F32S (p.Phe32Ser), rs2522301339, ClinGen CA414102038, ClinVar RCV003021782, Uncertain significance, Hereditary spastic paraplegia 2
- F32V (p.Phe32Val), UniProt VAR 015016, Pathogenic, in HLD1
- F32F (p.Phe32Phe), rs1309441892, gnomAD X-103785673-C-T, CADD 12.50
- C33F (p.Cys33Phe), rs1064794255, ClinGen CA414102051, ClinVar RCV002009750, ClinVar RCV003136402, AlphaMissense 0.99, MetaLR 0.98, Uncertain significance, Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2
- C33R (p.Cys33Arg), NCI-TCGA TCGA novel, Uncertain significance, Pelizaeus-Merzbacher disease
- C33Y (p.Cys33Tyr), rs1064794255, ClinGen CA16621168, ClinVar RCV000481592, UniProt VAR 046906, AlphaMissense 0.99, MetaLR 0.98, Likely pathogenic, not provided
- C33S (p.Cys33Ser), gnomAD X-103785675-G-C, CADD 26.00, PolyPhen-2 0.99
- C33C (p.Cys33Cys), rs2074489420, gnomAD X-103785676-T-C, CADD 13.30
- G34V (p.Gly34Val), rs778783545, ClinGen CA10478909, ClinVar RCV003622685, ExAC rs778783545, CADD 26.10, PolyPhen-2 1.00, Benign, Hereditary spastic paraplegia 2
- G34G (p.Gly34Gly), rs1429309917, gnomAD X-103785679-C-A, CADD 8.34
- C35* (p.Cys35Ter), rs2522301484, ClinVar RCV004595759, Likely pathogenic, in HLD1
- C35R (p.Cys35Arg), rs2522301460, ClinVar RCV004595749, UniProt VAR 046907, Likely pathogenic, Pelizaeus-Merzbacher disease
- C35Y (p.Cys35Tyr), rs1569427275, ClinGen CA414102070, ClinVar RCV000768444, ClinVar RCV003117551, AlphaMissense 0.99, MetaLR 0.98, Likely pathogenic, not provided
- G36E (p.Gly36Glu), cosmic curated COSV58277
- H37P (p.His37Pro), rs2522301501, ClinGen CA414102095, ClinVar RCV002437310, ClinVar RCV004595664, Conflicting interpretations, Inborn genetic diseases; Pelizaeus-Merzbacher disease
- A39D (p.Ala39Asp), rs2522301535, ClinGen CA414102119, ClinVar RCV003039156, Uncertain significance, Hereditary spastic paraplegia 2
- A39S (p.Ala39Ser), cosmic curated COSV10460
- A39T (p.Ala39Thr), cosmic curated COSV58276, UniProt VAR 015018, Pathogenic, in HLD1
- A39A (p.Ala39Ala), rs1261189615, gnomAD X-103785694-C-T, CADD 9.40
- L40F (p.Leu40Phe), cosmic curated COSV10515, CADD 24.10, PolyPhen-2 1.00
- L40H (p.Leu40His), rs2522301573, ClinVar RCV004595775, Likely pathogenic, Pelizaeus-Merzbacher disease
- L40L (p.Leu40Leu), rs1186741421, gnomAD X-103785697-C-G, CADD 8.47
- T41I (p.Thr41Ile), ExAC rs747978554, TOPMed rs747978554, gnomAD rs747978554, CADD 22.60, PolyPhen-2 0.02, Likely benign, Inborn genetic diseases
- T41P (p.Thr41Pro), rs1005010589, ClinVar RCV004595784, AlphaMissense 0.10, MetaLR 0.84, Likely pathogenic, Pelizaeus-Merzbacher disease
- T41S (p.Thr41Ser), TOPMed rs1005010589, AlphaMissense 0.10, MetaLR 0.84
- T41T (p.Thr41Thr), rs1262253168, gnomAD X-103785700-T-C, CADD 10.20
- G42D (p.Gly42Asp), rs2522301625, ClinVar RCV004595792, Likely pathogenic, Pelizaeus-Merzbacher disease
- G42G (p.Gly42Gly), rs896775245, gnomAD X-103785703-C-T, CADD 8.00
- T43I (p.Thr43Ile), rs132630289, ClinGen CA255704, ClinVar RCV000011835, UniProt VAR 004547, AlphaMissense 0.97, MetaLR 0.97, Pathogenic, in HLD1
- K45N (p.Lys45Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K45K (p.Lys45Lys), rs11543021, gnomAD X-103785712-G-A, CADD 7.50
- L46P (p.Leu46Pro), rs2522301673, ClinVar RCV004595808, UniProt VAR 015019, Likely pathogenic, Pelizaeus-Merzbacher disease
- L46R (p.Leu46Arg), UniProt VAR 015020, Pathogenic, in HLD1
- L46L (p.Leu46Leu), rs771833180, gnomAD X-103785715-A-G, CADD 8.23
- I47L (p.Ile47Leu), gnomAD rs1324241919, CADD 16.20, PolyPhen-2 0.04
- I47T (p.Ile47Thr), rs1060500909, ClinGen CA16616406, ClinVar RCV000463096, ClinVar RCV000681649, AlphaMissense 0.70, MetaLR 0.97, Likely pathogenic, Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2
- E48D (p.Glu48Asp), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10039, Variant assessed as somatic; moderate impact.
- T49A (p.Thr49Ala), gnomAD X-103785722-A-G, CADD 24.80, PolyPhen-2 0.99
- T49T (p.Thr49Thr), gnomAD X-103785724-C-A, CADD 7.12
- Y50C (p.Tyr50Cys), UniProt VAR 046908, Pathogenic, in HLD1
- Y50H (p.Tyr50His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in HLD1
- F51L (p.Phe51Leu), NCI-TCGA Cosmic COSV5827, cosmic curated COSV58277, Variant assessed as somatic; moderate impact., in HLD1
- F51S (p.Phe51Ser), UniProt VAR 015021, Pathogenic, in HLD1
- F51V (p.Phe51Val), rs2522301757, ClinVar RCV004595750, Likely pathogenic, Pelizaeus-Merzbacher disease
- S52S (p.Ser52Ser), gnomAD X-103785733-C-A, CADD 9.73
- K53N (p.Lys53Asn), cosmic curated COSV58278
- K53Q (p.Lys53Gln), rs2074490089, ClinGen CA414102264, ClinVar RCV001207491, Ensembl rs2074490089, AlphaMissense 0.24, MetaLR 0.96, Uncertain significance, Hereditary spastic paraplegia 2
- N54T (p.Asn54Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y55N (p.Tyr55Asn), gnomAD X-103785740-T-A, CADD 23.70, PolyPhen-2 0.90
- Q56* (p.Gln56Ter), rs1569427311, ClinGen CA414102309, ClinVar RCV000680072, Ensembl rs1569427311, Pathogenic
- Q56K (p.Gln56Lys), gnomAD X-103785743-C-A, CADD 22.40, PolyPhen-2 0.98
- Q56Q (p.Gln56Gln), rs2233697, gnomAD X-103785745-A-G, CADD 9.80
- D57N (p.Asp57Asn), rs132630296, ClinGen CA414102321, ClinVar RCV002296155, AlphaMissense 0.87, MetaLR 0.98, Uncertain significance, Hereditary spastic paraplegia 2
- D57Y (p.Asp57Tyr), rs132630296, ClinGen CA255715, ClinVar RCV000011848, Ensembl rs132630296, AlphaMissense 0.87, MetaLR 0.98, Pathogenic
- Y58C (p.Tyr58Cys), rs2074490307, ClinGen CA414102342, ClinVar RCV001196160, Ensembl rs2074490307, AlphaMissense 0.86, MetaLR 0.97, Pathogenic/Likely pathogenic, Pelizaeus-Merzbacher disease
- Y58* (p.Tyr58Ter), gnomAD X-103785751-T-G, CADD 34.00
- E59* (p.Glu59Ter), rs1060499653, ClinGen CA16609398, ClinVar RCV000449517, Ensembl rs1060499653, Pathogenic
- E59D (p.Glu59Asp), gnomAD rs1403370431, CADD 16.60, PolyPhen-2 0.76
- E59E (p.Glu59Glu), gnomAD X-103785754-G-A, CADD 6.61
- Y60* (p.Tyr60Ter), rs2522301939, ClinGen CA414102360, ClinVar RCV002922866, Pathogenic, in HLD1
- Y60C (p.Tyr60Cys), UniProt VAR 015022, Pathogenic, in HLD1
- L61I (p.Leu61Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L61V (p.Leu61Val), cosmic curated COSV10515
- L61L (p.Leu61Leu), gnomAD X-103785760-C-T, CADD 9.61
- I62N (p.Ile62Asn), Ensembl rs1021154717, Uncertain significance, not provided
- I62L (p.Ile62Leu), gnomAD X-103785761-A-C, CADD 20.60, PolyPhen-2 0.01
- I62T (p.Ile62Thr), gnomAD X-103785762-T-C, CADD 18.20, PolyPhen-2 0.14
- V64M (p.Val64Met), cosmic curated COSV58278, CADD 24.30, PolyPhen-2 0.91
- V64V (p.Val64Val), gnomAD X-103786465-G-A, CADD 19.40
- I65N (p.Ile65Asn), rs1191076247, ClinGen CA414102397, ClinVar RCV001924444, gnomAD rs1191076247, AlphaMissense 0.94, MetaLR 0.98, Uncertain significance, Hereditary spastic paraplegia 2
- I65S (p.Ile65Ser), rs1191076247, ClinGen CA414102399, ClinVar RCV001797040, ClinVar RCV003883703, AlphaMissense 0.94, MetaLR 0.98, Uncertain significance, not provided; Hereditary spastic paraplegia 2
- I65T (p.Ile65Thr), gnomAD rs1191076247, AlphaMissense 0.94, MetaLR 0.98, Uncertain significance
- I65V (p.Ile65Val), rs759106420, ClinGen CA10478944, ClinVar RCV001817515, ClinVar RCV003289101, CADD 21.40, PolyPhen-2 0.08, Uncertain significance, not specified; Inborn genetic diseases
- H66H (p.His66His), rs764723428, gnomAD X-103786471-T-C, CADD 10.60
- A67V (p.Ala67Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A67A (p.Ala67Ala), rs11543016, gnomAD X-103786474-C-A, CADD 8.12
- F68L (p.Phe68Leu), rs1483853759, ClinGen CA414102416, ClinVar RCV001977344, TOPMed rs1483853759, CADD 22.60, PolyPhen-2 0.04, Uncertain significance, Hereditary spastic paraplegia 2
- F68F (p.Phe68Phe), gnomAD X-103786477-C-T, CADD 12.60
- Q69* (p.Gln69Ter), rs2147764198, ClinGen CA414102425, ClinVar RCV001963109, Ensembl rs2147764198, Pathogenic
- Q69K (p.Gln69Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10039, Variant assessed as somatic; moderate impact.
- Q69L (p.Gln69Leu), rs2522306651, ClinVar RCV004595754, Likely pathogenic, Pelizaeus-Merzbacher disease
- Q69P (p.Gln69Pro), rs2522306651, ClinGen CA414102428, ClinVar RCV003512426, Uncertain significance, Hereditary spastic paraplegia 2
- V71D (p.Val71Asp), rs2522306682, ClinVar RCV004595755, Uncertain significance, Pelizaeus-Merzbacher disease
- V71V (p.Val71Val), gnomAD X-103786486-C-T, CADD 12.10
- I72F (p.Ile72Phe), TOPMed rs1237329577
- I72L (p.Ile72Leu), rs1237329577, ClinVar RCV004595366, AlphaMissense 0.85, MetaLR 0.98, Uncertain significance, Hereditary spastic paraplegia 2
- Y73Y (p.Tyr73Tyr), gnomAD X-103786492-T-C, CADD 10.40
- G74E (p.Gly74Glu), rs2522306764, ClinVar RCV004595756, Likely pathogenic, Pelizaeus-Merzbacher disease
- G74R (p.Gly74Arg), rs132630285, ClinGen CA255696, ClinVar RCV000011831, UniProt VAR 004548, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, in HLD1
- T75A (p.Thr75Ala), cosmic curated COSV10039
- T75P (p.Thr75Pro), rs2522306776, ClinVar RCV004595757, Uncertain significance, Pelizaeus-Merzbacher disease
- T75S (p.Thr75Ser), NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV5827, cosmic curated COSV58278, Variant assessed as somatic; moderate impact.
- T75I (p.Thr75Ile), gnomAD X-103786497-C-T, CADD 16.30, PolyPhen-2 0.02
- A76P (p.Ala76Pro), rs2147764222, ClinGen CA414102473, ClinVar RCV002272930, Ensembl rs2147764222, AlphaMissense 0.99, MetaLR 0.98, Likely pathogenic, Pelizaeus-Merzbacher disease
- A76A (p.Ala76Ala), gnomAD X-103786501-C-T, CADD 12.70
- S77P (p.Ser77Pro), rs2522306841, ClinGen CA414102479, ClinVar RCV003231827, Uncertain significance, not provided
- S77T (p.Ser77Thr), cosmic curated COSV58276
- S77Y (p.Ser77Tyr), rs2522306859, ClinVar RCV004595760, Uncertain significance, Pelizaeus-Merzbacher disease
- F80L (p.Phe80Leu), TOPMed rs903613007
- F80S (p.Phe80Ser), TOPMed rs2074498051, CADD 28.70, PolyPhen-2 1.00
- F80F (p.Phe80Phe), gnomAD X-103786513-C-T, CADD 13.10
- L81I (p.Leu81Ile), NCI-TCGA Cosmic COSV5827, cosmic curated COSV58276, Variant assessed as somatic; moderate impact.
- L81R (p.Leu81Arg), rs2522306943, ClinVar RCV004595761, Likely pathogenic, Pelizaeus-Merzbacher disease
- L81L (p.Leu81Leu), gnomAD X-103786516-T-C, CADD 11.50
- Y82C (p.Tyr82Cys), rs2147764248, ClinGen CA414102515, ClinVar RCV001848567, Ensembl rs2147764248, AlphaMissense 0.68, MetaLR 0.98, Uncertain significance, Hereditary spastic paraplegia
- Y82N (p.Tyr82Asn), cosmic curated COSV58277
- Y82Y (p.Tyr82Tyr), rs982694851, gnomAD X-103786519-T-C, CADD 10.50
- G83E (p.Gly83Glu), rs2522306997, ClinGen CA414102522, ClinVar RCV003864688, ClinVar RCV005936581, Uncertain significance, Hereditary spastic paraplegia 2
- A84S (p.Ala84Ser), rs1569427598, ClinGen CA414102527, ClinVar RCV002318682, ClinVar RCV004792426, CADD 24.10, PolyPhen-2 0.60, Uncertain significance, not provided; Inborn genetic diseases
- A84V (p.Ala84Val), rs2074498165, ClinGen CA414102530, cosmic curated COSV58276, ClinVar RCV003482802, CADD 19.90, PolyPhen-2 0.03, Uncertain significance, not provided
- L85H (p.Leu85His), rs2074498206, ClinGen CA414102536, ClinVar RCV001288681, Ensembl rs2074498206, AlphaMissense 0.99, MetaLR 0.98, Uncertain significance, not provided
- L85R (p.Leu85Arg), rs2074498206, ClinVar RCV004595762, ClinVar RCV005255786, AlphaMissense 0.99, MetaLR 0.98, Likely pathogenic, Pelizaeus-Merzbacher disease; not provided
- L85L (p.Leu85Leu), rs140047941, gnomAD X-103786528-C-T, CADD 9.76
- L86M (p.Leu86Met), gnomAD rs1416305526, CADD 23.50, PolyPhen-2 1.00
- L87P (p.Leu87Pro), rs2522307136, ClinVar RCV004595763, Likely pathogenic, Pelizaeus-Merzbacher disease
- L87L (p.Leu87Leu), rs758372406, gnomAD X-103786532-C-T, CADD 10.80
- E89D (p.Glu89Asp), TOPMed rs11543024, gnomAD rs11543024, Likely benign
- E89E (p.Glu89Glu), rs11543024, gnomAD X-103786540-G-A, CADD 10.30
Public PLP1 analysis runs
- PLP1 analysis run — PLP1 (564 variants) — completed 2026-08-22