MECP2 (Methyl-CpG-binding protein 2) variants and mutations
MECP2 (also known as Methyl-CpG-binding protein 2) is a human protein-coding gene encoding a methyl-CpG-binding protein 2 protein. It interprets DNA methylation and organizes transcriptional and chromatin states that are especially important in mature neurons. Loss-of-function variants cause Rett syndrome, whereas increased dosage causes MECP2 duplication syndrome. This analysis covers 1,324 MECP2 variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes Rett syndrome, X-linked intellectual disability-psychosis-macroorchidism syndrome, and severe neonatal-onset encephalopathy with microcephaly. Example MECP2 variants include M1L, M5I, and G7E.
Variant analysis overview
- Gene: MECP2
- Protein: Methyl-CpG-binding protein 2
- UniProt accession: P51608
- Organism: Homo sapiens
- Variants analyzed: 1324
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 928 unspecified-consequence records; 1 stop retained variant; 104 synonymous variants; 206 missense variants; 39 frameshift variants; 28 in-frame deletions; 6 in-frame insertions; 1 stop-gained variants; 1 stop lost; 6 substitution
- Prediction scores: 1,069 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Rett syndrome, X-linked intellectual disability-psychosis-macroorchidism syndrome, severe neonatal-onset encephalopathy with microcephaly, syndromic X-linked intellectual disability Lubs type, X-linked intellectual disability - psychosis - macroorchidism, atypical Rett syndrome, Angelman syndrome, Intellectual disability, hereditary disease, Neurodevelopmental delay, cancer, Seizure.
Protein structure and variant hotspots
- Protein features: 1 domains; 10 post-translational modification sites.
- Structural context: 146 variants have structural context.
- PTM context: 31 variants overlap post-translational modification sites.
- Experimental data: 72 protein positions have experimental scores. Source: binding assays.
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 MECP2 variants
Examples include M1L, M5I, G7E, L8P, R9S, R9T, R9X, E10*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs786205892, ClinGen CA274831, ClinVar RCV000172861, MetaLR 0.82, MetaSVM 0.35, Pathogenic, Rett syndrome
- M5I (p.Met5Ile), cosmic curated COSV10514, Ensembl rs2066832179, MetaLR 0.73, MetaSVM -0.01
- G7E (p.Gly7Glu), rs1057517905, ClinGen CA16043197, ClinVar RCV000413833, ClinVar RCV004786678, AlphaMissense 0.31, MetaLR 0.87, Pathogenic, not provided; Rett syndrome
- L8P (p.Leu8Pro), Ensembl rs1603340077, SIFT 0.01
- R9S (p.Arg9Ser), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57651, MetaLR 0.74, MetaSVM 0.67, Variant assessed as somatic; moderate impact.
- R9T (p.Arg9Thr), TOPMed rs2066831978
- R9X, rs786205042, Pathogenic
- E10* (p.Glu10Ter), rs61754421, ClinGen CA270320, ClinVar RCV000133050, Ensembl rs61754421, AlphaMissense 0.38, MetaLR 0.93, Likely pathogenic, in RTT
- E10Q (p.Glu10Gln), rs61754421, ClinGen CA270318, ClinVar RCV000133049, UniProt VAR 018180, AlphaMissense 0.38, MetaLR 0.93, Uncertain significance, Rett syndrome
- E11G (p.Glu11Gly), rs782735472, ClinGen CA10558666, ClinVar RCV002046520, ClinVar RCV003438912, AlphaMissense 0.24, MetaLR 0.91, Uncertain significance, not provided; Severe neonatal-onset encephalopathy with microcephaly
- K12N (p.Lys12Asn), rs61754422, ClinGen CA170293, ClinVar RCV000133081, ClinVar RCV003389405, AlphaMissense 0.44, MetaLR 0.83, Uncertain significance, not provided
- K12R (p.Lys12Arg), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57654, SIFT 0.10, Variant assessed as somatic; moderate impact.
- S13* (p.Ser13Ter), rs2148667313, ClinGen CA415179115, ClinVar RCV001384305, ClinVar RCV004698352, Pathogenic
- S13A (p.Ser13Ala), rs2065992065, ClinGen CA415179127, ClinVar RCV001339324, Ensembl rs2065992065, AlphaMissense 0.06, MetaLR 0.86, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- S10RfsX36, rs797045693, Pathogenic
- E14K (p.Glu14Lys), rs2065991940, ClinGen CA415179104, ClinVar RCV002274717, TOPMed rs2065991940, AlphaMissense 0.36, MetaLR 0.94, Uncertain significance, not provided
- E14Q (p.Glu14Gln), TOPMed rs2065991940, gnomAD rs2065991940, Uncertain significance
- D15A (p.Asp15Ala), rs1557138051, ClinGen CA415179037, ClinVar RCV001317181, gnomAD rs1557138051, AlphaMissense 0.36, MetaLR 0.93, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- Q16* (p.Gln16Ter), rs61754424, ClinGen CA232975, ClinVar RCV000133124, ClinVar RCV003389406, Pathogenic
- D17E (p.Asp17Glu), gnomAD rs1557138037, Likely benign
- D17G (p.Asp17Gly), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57657, SIFT 0.76, Variant assessed as somatic; moderate impact.
- L18F (p.Leu18Phe), rs2065991510, ClinGen CA415178969, ClinVar RCV001340158, ClinVar RCV001806131, AlphaMissense 0.10, MetaLR 0.93, Uncertain significance, not provided; Severe neonatal-onset encephalopathy with microcephaly
- L18P (p.Leu18Pro), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, SIFT 0.05, Variant assessed as somatic; moderate impact.
- Q19* (p.Gln19Ter), rs61754425, ClinGen CA270467, ClinVar RCV000133160, ClinVar RCV002316919, AlphaMissense 0.09, MetaLR 0.82, Pathogenic
- Q19E (p.Gln19Glu), rs61754425, ClinGen CA415178943, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57652, AlphaMissense 0.09, MetaLR 0.82, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- Q19H (p.Gln19His), rs2148667234, ClinGen CA415178887, ClinVar RCV001883929, Ensembl rs2148667234, AlphaMissense 0.20, MetaLR 0.89, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- Q19P (p.Gln19Pro), rs2148667246, ClinGen CA415178909, ClinVar RCV001872798, Ensembl rs2148667246, AlphaMissense 0.10, MetaLR 0.90, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- G20R (p.Gly20Arg), rs1557138023, ClinGen CA415178871, ClinVar RCV000500533, gnomAD rs1557138023, AlphaMissense 0.10, MetaLR 0.85, Uncertain significance, not specified
- G20S (p.Gly20Ser), rs1557138023, ClinGen CA415178875, ClinVar RCV003860690, gnomAD rs1557138023, AlphaMissense 0.10, MetaLR 0.85, Likely benign, Severe neonatal-onset encephalopathy with microcephaly
- G20G (p.Gly20Gly), rs786205045, Pathogenic
- L21F (p.Leu21Phe), rs782396283, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, ExAC rs782396283, AlphaMissense 0.11, MetaLR 0.82, Variant assessed as somatic; moderate impact.
- L21H (p.Leu21His), 1000Genomes rs1410143595, TOPMed rs1410143595
- L21P (p.Leu21Pro), 1000Genomes rs1410143595, TOPMed rs1410143595, REVEL 0.34, CADD 28.40
- K22* (p.Lys22Ter), rs62641234, ClinGen CA270495, ClinVar RCV000133187, Ensembl rs62641234, Pathogenic
- D23E (p.Asp23Glu), rs781974856, ClinGen CA10558659, ClinVar RCV003314837, ClinVar RCV003523156, AlphaMissense 0.13, MetaLR 0.89, Likely benign, Rett syndrome
- K24R (p.Lys24Arg), rs782344115, ClinGen CA10558658, ClinVar RCV000807863, ExAC rs782344115, AlphaMissense 0.12, MetaLR 0.92, Benign, Severe neonatal-onset encephalopathy with microcephaly
- P25A (p.Pro25Ala), TOPMed rs1275570991, gnomAD rs1275570991, Uncertain significance
- P25S (p.Pro25Ser), rs1275570991, ClinGen CA415178714, ClinVar RCV001769336, TOPMed rs1275570991, AlphaMissense 0.08, MetaLR 0.82, Uncertain significance, not provided
- P25T (p.Pro25Thr), TOPMed rs1275570991, gnomAD rs1275570991, Uncertain significance
- L26F (p.Leu26Phe), rs1603310890, ClinGen CA415178680, ClinVar RCV003864667, AlphaMissense 0.06, MetaLR 0.77, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- L26V (p.Leu26Val), rs1603310890, ClinGen CA415178685, ClinVar RCV000795931, Ensembl rs1603310890, AlphaMissense 0.06, MetaLR 0.77, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- F28L (p.Phe28Leu), rs1557137994, ClinGen CA415178627, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, AlphaMissense 0.41, MetaLR 0.69, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- F28V (p.Phe28Val), cosmic curated COSV57652
- K30T (p.Lys30Thr), Ensembl rs2065990170
- K32N (p.Lys32Asn), NCI-TCGA TCGA novel, MetaLR 0.90, MetaSVM 0.88, Variant assessed as somatic; moderate impact.
- K33T (p.Lys33Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D34Y (p.Asp34Tyr), rs2522112911, ClinGen CA415178460, ClinVar RCV003020611, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- K35E (p.Lys35Glu), rs2522112759, ClinGen CA415178434, ClinVar RCV003063909, Benign, Severe neonatal-onset encephalopathy with microcephaly
- K39R (p.Lys39Arg), TOPMed rs2065989454, MetaLR 0.94, MetaSVM 1.11, Uncertain significance, Inborn genetic diseases; not provided; Severe neonatal-onset encephalopathy with
- G41S (p.Gly41Ser), cosmic curated COSV57656, Uncertain significance, not provided
- K42Q (p.Lys42Gln), TOPMed rs1438755884, MetaLR 0.94, MetaSVM 0.97, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- V46L (p.Val46Leu), ExAC rs587783134, TOPMed rs587783134, gnomAD rs587783134, Likely benign, Inborn genetic diseases
- V46M (p.Val46Met), rs587783134, ClinGen CA294698, ClinVar RCV000144806, ClinVar RCV002055865, AlphaMissense 0.09, MetaLR 0.72, Benign/Likely benign, Inborn genetic diseases; not provided; Severe neonatal-onset encephalopathy with
- Q47L (p.Gln47Leu), cosmic curated COSV57652
- Q47R (p.Gln47Arg), cosmic curated COSV57656, MetaLR 0.78, MetaSVM 0.58
- P48Q (p.Pro48Gln), rs1557137939, gnomAD rs1557137939, AlphaMissense 0.10, MetaLR 0.93, Variant assessed as somatic; moderate impact.
- S49* (p.Ser49Ter), rs61754432, ClinGen CA232954, ClinVar RCV000133023, ClinVar RCV000192902, Pathogenic
- A50G (p.Ala50Gly), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Variant assessed as somatic; moderate impact.
- A50T (p.Ala50Thr), cosmic curated COSV57656
- A50V (p.Ala50Val), TOPMed rs1480424905, gnomAD rs1480424905, MetaLR 0.84, MetaSVM 0.60
- H51Q (p.His51Gln), rs267608432, ClinGen CA170260, ClinVar RCV000133024, ClinVar RCV001857482, AlphaMissense 0.10, MetaLR 0.81, Uncertain significance, Rett syndrome
- H52Q (p.His52Gln), rs781819534, ClinGen CA10558653, ClinVar RCV001480968, ClinVar RCV001576872, AlphaMissense 0.08, MetaLR 0.63, Likely benign, Severe neonatal-onset encephalopathy with microcephaly; not provided
- H52R (p.His52Arg), rs61754433, ClinGen CA170263, ClinVar RCV000133025, ClinVar RCV001520931, AlphaMissense 0.08, MetaLR 0.71, Benign, Rett syndrome
- S53C (p.Ser53Cys), cosmic curated COSV10588
- A54S (p.Ala54Ser), TOPMed rs2065988294
- A54V (p.Ala54Val), TOPMed rs2065988229, MetaLR 0.83, MetaSVM 0.69, Uncertain significance, Inborn genetic diseases; not provided
- E55D (p.Glu55Asp), cosmic curated COSV57653
- A57T (p.Ala57Thr), cosmic curated COSV10031, Ensembl rs2148666914, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- A57V (p.Ala57Val), ExAC rs782432972, MetaLR 0.80, MetaSVM 0.47
- A59T (p.Ala59Thr), cosmic curated COSV57654, gnomAD rs1557137911
- G60D (p.Gly60Asp), rs2148666907, ClinGen CA415177646, cosmic curated COSV57653, ClinVar RCV001378002, AlphaMissense 0.42, MetaLR 0.85, Likely pathogenic, Severe neonatal-onset encephalopathy with microcephaly
- G60S (p.Gly60Ser), rs2522111128, ClinGen CA415177654, ClinVar RCV003023622, Pathogenic, Severe neonatal-onset encephalopathy with microcephaly
- E63K (p.Glu63Lys), NCI-TCGA TCGA novel, MetaLR 0.81, MetaSVM 0.51, Variant assessed as somatic; moderate impact.
- S65* (p.Ser65Ter), rs61754437, ClinGen CA415177559, ClinVar RCV001048131, Ensembl rs61754437, AlphaMissense 0.09, MetaLR 0.79, Pathogenic
- S65L (p.Ser65Leu), rs61754437, ClinGen CA415177555, ClinVar RCV001007927, Ensembl rs61754437, AlphaMissense 0.09, MetaLR 0.79, Pathogenic, Rett syndrome
- G67V (p.Gly67Val), rs150900180, ClinGen CA337265756, ClinVar RCV001196929, ClinVar RCV002559252, AlphaMissense 0.08, MetaLR 0.78, Uncertain significance, Inborn genetic diseases; Severe neonatal-onset encephalopathy with microcephaly
- G67W (p.Gly67Trp), ExAC rs782797297, gnomAD rs782797297
- S68* (p.Ser68Ter), rs267608438, ClinGen CA270298, ClinVar RCV000133031, ClinVar RCV001814066, AlphaMissense 0.08, MetaLR 0.81, Pathogenic
- S68L (p.Ser68Leu), gnomAD rs267608438, MetaLR 0.92, MetaSVM 1.09, Pathogenic
- G69V (p.Gly69Val), rs1557137890, ClinGen CA415177513, ClinVar RCV001770566, ClinVar RCV002540260, AlphaMissense 0.09, MetaLR 0.82, Uncertain significance, Rett syndrome
- S70C (p.Ser70Cys), rs2065987230, ClinGen CA415177498, ClinVar RCV001216969, Ensembl rs2065987230, AlphaMissense 0.12, MetaLR 0.79, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- S70P (p.Ser70Pro), rs1557137884, ClinGen CA415177504, ClinVar RCV000678236, ClinVar RCV003638701, AlphaMissense 0.12, MetaLR 0.76, Uncertain significance, Rett syndrome
- S70Y (p.Ser70Tyr), cosmic curated COSV10814, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A71D (p.Ala71Asp), rs1557137874, ClinGen CA415177482, ClinVar RCV002109086, ClinVar RCV005375055, AlphaMissense 0.13, MetaLR 0.85, Conflicting interpretations, Inborn genetic diseases; Severe neonatal-onset encephalopathy with microcephaly
- A71G (p.Ala71Gly), rs1557137874, ClinGen CA415177484, ClinVar RCV001361402, ClinVar RCV004728670, AlphaMissense 0.13, MetaLR 0.85, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- A71T (p.Ala71Thr), Ensembl rs2065987061, REVEL 0.46, MetaLR 0.84
- A71V (p.Ala71Val), rs1557137874, ClinGen CA415177479, ClinVar RCV002859257, ClinVar RCV003135248, AlphaMissense 0.13, MetaLR 0.85, Uncertain significance, Inborn genetic diseases; not provided
- P72L (p.Pro72Leu), rs61754440, ClinGen CA170269, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57652, AlphaMissense 0.14, MetaLR 0.73, Likely benign, Rett syndrome
- P72S (p.Pro72Ser), ExAC rs781859649, gnomAD rs781859649, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- A73P (p.Ala73Pro), Ensembl rs2148666775
- A73V (p.Ala73Val), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57651, MetaLR 0.86, MetaSVM 0.89, Variant assessed as somatic; moderate impact.
- P75A (p.Pro75Ala), cosmic curated COSV10814
- P75L (p.Pro75Leu), rs267608440, ClinGen CA170272, ClinVar RCV000133035, ClinVar RCV000195208, AlphaMissense 0.24, MetaLR 0.89, Benign, Rett syndrome
- E76K (p.Glu76Lys), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Variant assessed as somatic; moderate impact.
- S78A (p.Ser78Ala), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.83, MetaSVM 0.84, Variant assessed as somatic; moderate impact.
- A79S (p.Ala79Ser), rs1557137845, ClinGen CA415177391, ClinVar RCV000587702, Ensembl rs1557137845, AlphaMissense 0.13, MetaLR 0.80, Uncertain significance, not provided
- A79V (p.Ala79Val), ExAC rs782136314, TOPMed rs782136314, gnomAD rs782136314, MetaLR 0.78, MetaSVM 0.30
- S80C (p.Ser80Cys), rs1332969540, ClinGen CA415177339, ClinVar RCV000678234, TOPMed rs1332969540, AlphaMissense 0.54, MetaLR 0.84, Uncertain significance, not provided
- S80F (p.Ser80Phe), rs1332969540, ClinGen CA415177336, ClinVar RCV002304683, ClinVar RCV003438994, AlphaMissense 0.54, MetaLR 0.84, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly; not provided
- K82* (p.Lys82Ter), rs1603310794, ClinGen CA415177310, ClinVar RCV000816083, Ensembl rs1603310794, Pathogenic
- K82N (p.Lys82Asn), NCI-TCGA TCGA novel, Likely pathogenic, Focal epilepsy; Rett syndrome
- K82R (p.Lys82Arg), rs61754444, ClinGen CA170278, ClinVar RCV000133040, ClinVar RCV000981151, AlphaMissense 0.17, MetaLR 0.79, Pathogenic/Likely pathogenic, Severe neonatal-onset encephalopathy with microcephaly; Rett syndrome
- Q83* (p.Gln83Ter), rs2148666695, ClinGen CA415177286, ClinVar RCV001939126, Ensembl rs2148666695, Pathogenic
- Q83R (p.Gln83Arg), TOPMed rs2065985983, gnomAD rs2065985983, MetaLR 0.87, MetaSVM 0.83
- R84Q (p.Arg84Gln), rs797044707, ClinGen CA243342, ClinVar RCV000177221, Ensembl rs797044707, AlphaMissense 0.97, MetaLR 0.87, Uncertain significance, not provided
- R84W (p.Arg84Trp), rs1557137821, ClinGen CA415177265, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57657, AlphaMissense 0.99, MetaLR 0.89, Uncertain significance, MECP2-related disorder; Severe neonatal-onset encephalopathy with microcephaly
- R85C (p.Arg85Cys), rs1064797047, ClinGen CA16621248, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57651, AlphaMissense 0.99, MetaLR 0.89, Uncertain significance, Rett syndrome
- R85H (p.Arg85His), rs782226571, ClinGen CA10558645, cosmic curated COSV57651, ClinVar RCV001047333, AlphaMissense 0.96, MetaLR 0.84, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- S86C (p.Ser86Cys), rs61754445, ClinGen CA270305, ClinVar RCV000133041, UniProt VAR 018181, AlphaMissense 0.95, MetaLR 0.88, Uncertain significance, Rett syndrome
- I88T (p.Ile88Thr), NCI-TCGA TCGA novel, MetaLR 0.84, MetaSVM 0.70, Variant assessed as somatic; moderate impact.
- R89C (p.Arg89Cys), rs782601477, ClinGen CA10558644, ClinVar RCV001561656, ClinVar RCV002318251, AlphaMissense 1.00, MetaLR 0.88, Benign, Rett syndrome
- R89H (p.Arg89His), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57652, Variant assessed as somatic; moderate impact.
- R89S (p.Arg89Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D90H (p.Asp90His), rs2522109031, ClinGen CA415177164, ClinVar RCV003522765, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- R91P (p.Arg91Pro), rs782177397, ClinGen CA415177145, ClinVar RCV003639717, ClinVar RCV003988136, AlphaMissense 0.97, MetaLR 0.88, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- R91Q (p.Arg91Gln), rs782177397, ClinGen CA10558642, ClinVar RCV001297075, ClinVar RCV003485703, AlphaMissense 0.97, MetaLR 0.88, Uncertain significance, Rett syndrome; Severe neonatal-onset encephalopathy with microcephaly
- R91W (p.Arg91Trp), rs782320257, ClinGen CA10558643, cosmic curated COSV57656, ClinVar RCV001539474, AlphaMissense 0.99, MetaLR 0.85, Uncertain significance, not provided; Severe neonatal-onset encephalopathy with microcephaly
- G92* (p.Gly92Ter), rs267608445, ClinGen CA270309, ClinVar RCV000133043, ClinVar RCV005886948, Likely pathogenic
- G92E (p.Gly92Glu), rs2148666605, ClinGen CA415177118, ClinVar RCV001941309, Ensembl rs2148666605, AlphaMissense 1.00, MetaLR 0.86, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- P93S (p.Pro93Ser), rs61754447, ClinGen CA270313, ClinVar RCV000133046, ClinVar RCV005089656, AlphaMissense 1.00, MetaLR 0.96, Conflicting interpretations, X-linked MECP2-related disorders; Severe neonatal-onset encephalopathy with micr
- M94I (p.Met94Ile), cosmic curated COSV57655
- M94L (p.Met94Leu), NCI-TCGA TCGA novel, MetaLR 0.83, MetaSVM 0.59, Variant assessed as somatic; moderate impact.
- D97E (p.Asp97Glu), rs61754449, ClinGen CA270323, ClinVar RCV000133051, UniProt VAR 023552, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, Rett syndrome
- D97Y (p.Asp97Tyr), rs61754448, ClinGen CA270316, ClinVar RCV000133048, UniProt VAR 018182, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Rett syndrome
- P98H (p.Pro98His), NCI-TCGA TCGA novel, MetaLR 0.86, MetaSVM 0.92, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- T99P (p.Thr99Pro), rs2065984609, ClinGen CA415176953, ClinVar RCV001065758, ClinVar RCV001507069, AlphaMissense 0.99, MetaLR 0.94, Uncertain significance, Rett syndrome
- L100R (p.Leu100Arg), rs61754451, ClinGen CA270326, ClinVar RCV000133055, UniProt VAR 023553, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, Rett syndrome
- L100V (p.Leu100Val), rs28935168, ClinGen CA198822, ClinVar RCV000012608, ClinVar RCV000498874, AlphaMissense 0.98, MetaLR 0.99, Pathogenic, Rett syndrome
- P101H (p.Pro101His), rs61754453, ClinGen CA270330, ClinVar RCV000133057, UniProt VAR 018183, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Rett syndrome
- P101L (p.Pro101Leu), rs61754453, ClinGen CA270332, ClinVar RCV000133059, UniProt VAR 018184, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Rett syndrome
- P101R (p.Pro101Arg), rs61754453, ClinGen CA274626, ClinVar RCV000133058, ClinVar RCV000170238, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, Rett syndrome
- P101S (p.Pro101Ser), rs61754452, ClinGen CA270328, ClinVar RCV000133056, UniProt VAR 023554, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, Rett syndrome
- P101T (p.Pro101Thr), rs61754452, ClinGen CA415176913, ClinVar RCV001782431, UniProt VAR 018185, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, not provided
- E102K (p.Glu102Lys), NCI-TCGA Cosmic COSV5765, cosmic curated COSV57656, MetaLR 0.73, MetaSVM 0.26, Variant assessed as somatic; moderate impact.
- G103D (p.Gly103Asp), rs267608450, ClinGen CA270334, ClinVar RCV000133060, ClinVar RCV002222406, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not specified; Rett syndrome
- G103S (p.Gly103Ser), rs2065984147, ClinGen CA415176886, ClinVar RCV001070837, Ensembl rs2065984147, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- G103V (p.Gly103Val), NCI-TCGA TCGA novel, MetaLR 0.88, MetaSVM 1.00, Variant assessed as somatic; moderate impact.
- W104* (p.Trp104Ter), rs61754455, ClinGen CA270340, cosmic curated COSV57655, ClinVar RCV000133062, Pathogenic
- W104C (p.Trp104Cys), rs1557137745, ClinGen CA415176854, ClinVar RCV000624621, Ensembl rs1557137745, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, Inborn genetic diseases
- W104G (p.Trp104Gly), rs267608451, ClinGen CA415176868, ClinVar RCV004528687, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, MECP2-related disorder
- W104R (p.Trp104Arg), rs267608451, ClinGen CA270337, ClinVar RCV000133061, Ensembl rs267608451, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, Rett syndrome
- T105P (p.Thr105Pro), rs1060499623, ClinGen CA16609354, ClinVar RCV000445577, Ensembl rs1060499623, AlphaMissense 0.99, MetaLR 0.97, Uncertain significance, not specified
- R106G (p.Arg106Gly), rs28934907, ClinGen CA270345, ClinVar RCV000133065, ClinVar RCV004532600, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, MECP2-related disorder; Rett syndrome
- R106L (p.Arg106Leu), rs61754457, ClinGen CA270350, ClinVar RCV000133068, ClinVar RCV001843481, AlphaMissense 1.00, MetaLR 0.99, Pathogenic/Likely pathogenic, not provided; Rett syndrome
- R106Q (p.Arg106Gln), rs61754457, ClinGen CA270348, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57653, AlphaMissense 1.00, MetaLR 0.99, Pathogenic/Likely pathogenic, Inborn genetic diseases; X-linked intellectual disability-psychosis-macroorchidi
- R106W (p.Arg106Trp), rs28934907, ClinGen CA256089, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57654, AlphaMissense 1.00, MetaLR 0.99, Pathogenic/Likely pathogenic, MECP2-related disorder; Inborn genetic diseases; not specified
- K107N (p.Lys107Asn), cosmic curated COSV57652
- K107R (p.Lys107Arg), rs2148666479, ClinGen CA415176830, ClinVar RCV001906666, Ensembl rs2148666479, AlphaMissense 0.37, MetaLR 0.95, Uncertain significance, not specified
- L108F (p.Leu108Phe), rs1557137721, ClinGen CA415176801, ClinVar RCV001036360, gnomAD rs1557137721, AlphaMissense 0.96, MetaLR 0.89, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- L108H (p.Leu108His), rs61754458, ClinGen CA270353, ClinVar RCV000133069, Ensembl rs61754458, AlphaMissense 1.00, MetaLR 0.97, Likely pathogenic, Rett syndrome
- L108P (p.Leu108Pro), rs61754458, ClinGen CA294701, ClinVar RCV003223521, Ensembl rs61754458, AlphaMissense 1.00, MetaLR 0.97, Likely pathogenic, Rett syndrome
- L108V (p.Leu108Val), rs1557137721, ClinGen CA415176805, ClinVar RCV001915903, gnomAD rs1557137721, AlphaMissense 0.96, MetaLR 0.89, Uncertain significance, Severe neonatal-onset encephalopathy with microcephaly
- K109E (p.Lys109Glu), rs886041732, ClinGen CA10603536, ClinVar RCV000314570, Ensembl rs886041732, AlphaMissense 1.00, MetaLR 0.97, Pathogenic, not provided
- R111G (p.Arg111Gly), rs61754459, ClinGen CA270357, ClinVar RCV000133071, UniProt VAR 018187, AlphaMissense 1.00, MetaLR 0.97, Likely pathogenic, Rett syndrome
- R111K (p.Arg111Lys), rs1057518718, ClinGen CA16043705, ClinVar RCV000415409, ClinVar RCV003144255, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, not provided
- R111T (p.Arg111Thr), rs1057518718, ClinGen CA415176724, ClinVar RCV003640345, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, Severe neonatal-onset encephalopathy with microcephaly
- K112* (p.Lys112Ter), rs267608398, ClinGen CA232962, ClinVar RCV000133072, ClinVar RCV004527359, Pathogenic
- K112E (p.Lys112Glu), cosmic curated COSV10031
- S113F (p.Ser113Phe), rs781871640, NCI-TCGA Cosmic COSV1003, ExAC rs781871640, gnomAD rs781871640, AlphaMissense 1.00, MetaLR 0.98, Variant assessed as somatic; moderate impact.
- S113Y (p.Ser113Tyr), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.98, MetaSVM 1.08, Variant assessed as somatic; moderate impact.
- G114A (p.Gly114Ala), rs61755760, ClinGen CA270359, ClinVar RCV000133073, ClinVar RCV005860009, AlphaMissense 1.00, MetaLR 0.99, Conflicting interpretations, Syndromic X-linked intellectual disability Lubs type; Rett syndrome
- R115C (p.Arg115Cys), rs267608388, ClinGen CA294544, ClinVar RCV000133074, ClinVar RCV000715718, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, Rett syndrome
- R115H (p.Arg115His), rs782638331, ClinGen CA10558640, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57653, AlphaMissense 1.00, MetaLR 0.97, Pathogenic, Rett syndrome
- A117G (p.Ala117Gly), rs2522106660, ClinGen CA415176615, ClinVar RCV003155620, Likely pathogenic, Rett syndrome
- G118A (p.Gly118Ala), rs1557137672, ClinGen CA415176592, ClinVar RCV000498617, Ensembl rs1557137672, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, not provided
- G118E (p.Gly118Glu), rs1557137672, ClinVar RCV004557299, ClinVar RCV005054003, AlphaMissense 1.00, MetaLR 0.98, Pathogenic, Rett syndrome
- G118W (p.Gly118Trp), cosmic curated COSV10031, MetaLR 0.99, MetaSVM 1.04
- Y120C (p.Tyr120Cys), rs2522106547, NCI-TCGA Cosmic COSV5765, cosmic curated COSV57657, ClinGen CA415176540, Pathogenic, not provided
- Y120D (p.Tyr120Asp), rs267608454, ClinGen CA270363, ClinVar RCV000133076, UniProt VAR 023555, AlphaMissense 1.00, MetaLR 0.96, Uncertain significance, Rett syndrome
- D121E (p.Asp121Glu), rs2065982277, ClinGen CA415176490, ClinVar RCV001810713, Ensembl rs2065982277, AlphaMissense 1.00, MetaLR 0.91, Benign, not provided
- D121G (p.Asp121Gly), rs61755762, ClinGen CA170287, ClinVar RCV000133078, ClinVar RCV003990984, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, Rett syndrome
- D121H (p.Asp121His), rs2522106457, ClinGen CA415176516, ClinVar RCV004421695, Likely pathogenic, Inborn genetic diseases
- D121V (p.Asp121Val), rs61755762, ClinGen CA415176492, ClinVar RCV001420143, Ensembl rs61755762, AlphaMissense 1.00, MetaLR 0.96, Likely pathogenic, Rett syndrome
- V122A (p.Val122Ala), rs267608456, ClinGen CA170290, ClinVar RCV000133080, ClinVar RCV003483517, AlphaMissense 1.00, MetaLR 0.98, Uncertain significance, Rett syndrome
- V122M (p.Val122Met), rs267608455, ClinGen CA270366, ClinVar RCV000133079, ClinVar RCV000254852, AlphaMissense 1.00, MetaLR 0.99, Pathogenic, Rett syndrome
- L124F (p.Leu124Phe), rs61755763, ClinGen CA270369, ClinVar RCV000133082, UniProt VAR 010277, AlphaMissense 1.00, MetaLR 0.93, Pathogenic, Rett syndrome
- L124V (p.Leu124Val), rs2148666355, ClinGen CA415176431, ClinVar RCV002006896, Ensembl rs2148666355, AlphaMissense 0.93, MetaLR 0.95, Likely pathogenic, Severe neonatal-onset encephalopathy with microcephaly
- N126D (p.Asn126Asp), rs1064796513, ClinGen CA16621247, ClinVar RCV000478123, Ensembl rs1064796513, AlphaMissense 0.95, MetaLR 0.96, Uncertain significance, not provided
- N126I (p.Asn126Ile), rs786205037, ClinGen CA415176375, ClinVar RCV003484978, AlphaMissense 0.31, MetaLR 0.87, Likely pathogenic, Rett syndrome
- N126S (p.Asn126Ser), rs786205037, ClinGen CA280064, ClinVar RCV000170271, ClinVar RCV003991024, AlphaMissense 0.31, MetaLR 0.87, Uncertain significance, Rett syndrome
Public MECP2 analysis runs
- MECP2 analysis run — MECP2 (1,324 variants) — completed 2026-08-18