NF1 (Neurofibromin) variants and mutations
NF1 (also known as Neurofibromin) is a human protein-coding gene encoding a neurofibromin protein. It accelerates conversion of active RAS-GTP to inactive RAS-GDP and therefore restrains RAS-MAPK signaling. Loss-of-function variants cause neurofibromatosis type 1 with neurofibromas, pigmentary features, learning difficulties, and increased tumor risk. This analysis covers 13,101 NF1 variants and mutations. Of these, 54% have computational variant effect predictions. Disease context includes neurofibromatosis type 1, neurofibromatosis-Noonan syndrome, and neurofibromatosis. Example NF1 variants include M1?, M1I, and M1K.
Variant analysis overview
- Gene: NF1
- Protein: Neurofibromin
- UniProt accession: P21359
- Organism: Homo sapiens
- Variants analyzed: 13101
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 13,033 unspecified-consequence records; 39 synonymous variants; 23 missense variants; 2 frameshift variants; 1 in-frame insertions; 2 splice-region variants; 1 substitution
- Prediction scores: 7,093 variants have prediction scores (54% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurofibromatosis type 1, neurofibromatosis-Noonan syndrome, neurofibromatosis, juvenile myelomonocytic leukemia, Watson syndrome, neurofibromatosis, familial spinal, malignant peripheral nerve sheath tumor, Neurofibromatosis type 1 due to NF1mutation or intragenic deletion, Tibial pseudarthrosis, neurocutaneous syndrome, neurofibroma, rhabdomyosarcoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 14 post-translational modification sites.
- Structural context: 1,823 variants have structural context.
- PTM context: 62 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 NF1 variants
Examples include M1?, M1I, M1K, M1L, M1R, M1T, M1V, A2D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV6221, cosmic curated COSV62212, Variant assessed as somatic; high impact.
- M1I (p.Met1Ile), rs1598173737, ClinGen CA398979155, ClinVar RCV002319303, ClinVar RCV005639237, MetaLR 0.08, MetaSVM -1.12, Pathogenic/Likely pathogenic, Neurofibromatosis, type 1; Juvenile myelomonocytic leukemia; Neurofibromatosis-N
- M1K (p.Met1Lys), rs886041346, ClinGen CA398979146, ClinVar RCV000659954, ClinVar RCV001090740, MetaLR 0.08, MetaSVM -1.08, Pathogenic
- M1L (p.Met1Leu), rs1060500252, ClinGen CA398979144, ClinVar RCV001939653, ClinVar RCV002423137, MetaLR 0.07, MetaSVM -1.11, Pathogenic
- M1R (p.Met1Arg), rs886041346, ClinGen CA398979149, ClinVar RCV000489359, ClinVar RCV001387996, MetaLR 0.08, MetaSVM -1.08, Pathogenic
- M1T (p.Met1Thr), rs886041346, ClinGen CA10603591, ClinVar RCV000324649, ClinVar RCV001855057, MetaLR 0.08, MetaSVM -1.08, Pathogenic
- M1V (p.Met1Val), rs1060500252, ClinGen CA16615129, ClinVar RCV000476863, ClinVar RCV001556803, MetaLR 0.07, MetaSVM -1.11, Pathogenic
- A2D (p.Ala2Asp), rs1555594473, ClinGen CA398979165, ClinVar RCV002948460, ClinVar RCV003225245, AlphaMissense 0.93, MetaLR 0.08, Uncertain significance
- A2F (p.Ala2Phe), rs1555594471, ClinGen CA658658569, ClinVar RCV000632482, ClinVar RCV002315794, Uncertain significance
- A2G (p.Ala2Gly), Ensembl rs1555594473, Uncertain significance
- A2S (p.Ala2Ser), rs2143144232, ClinGen CA398979164, ClinVar RCV001997805, ClinVar RCV002344125, REVEL 0.09, AlphaMissense 0.32, Uncertain significance
- A2T (p.Ala2Thr), rs2143144232, ClinGen CA398979159, ClinVar RCV003599133, Ensembl rs2143144232, AlphaMissense 0.32, MetaLR 0.07, Uncertain significance, Neurofibromatosis, type 1
- A2V (p.Ala2Val), rs1555594473, ClinGen CA398979169, ClinVar RCV000564452, ClinVar RCV006612389, REVEL 0.10, AlphaMissense 0.93, Uncertain significance
- A2A (p.Ala2Ala), gnomAD 17-31095315-C-A, CADD 19.30
- A3E (p.Ala3Glu), rs1911550821, ClinGen CA398979177, ClinVar RCV002376340, REVEL 0.13, AlphaMissense 0.58, Uncertain significance
- A3G (p.Ala3Gly), rs1911550821, ClinGen CA398979179, ClinVar RCV001340220, Ensembl rs1911550821, AlphaMissense 0.58, MetaLR 0.06, Uncertain significance
- A3P (p.Ala3Pro), Ensembl rs1598173770, Uncertain significance
- A3R (p.Ala3Arg), rs2143144314, ClinGen CA2499223965, ClinVar RCV001380139, Pathogenic
- A3T (p.Ala3Thr), rs1598173770, ClinGen CA398979175, ClinVar RCV000815492, ClinVar RCV002422823, REVEL 0.17, MetaLR 0.03, Uncertain significance
- A3V (p.Ala3Val), rs1911550821, ClinGen CA398979181, cosmic curated COSV62201, ClinVar RCV001223014, REVEL 0.13, AlphaMissense 0.58, Uncertain significance
- A3S (p.Ala3Ser), gnomAD 17-31095316-G-T, REVEL 0.15, MetaLR 0.06
- A3A (p.Ala3Ala), gnomAD 17-31095318-G-T, CADD 17.00
- H4N (p.His4Asn), rs1911551060, ClinGen CA398979184, ClinVar RCV001056212, TOPMed rs1911551060, REVEL 0.06, MetaLR 0.02, Uncertain significance
- H4Q (p.His4Gln), Ensembl rs2143144553, REVEL 0.07, MetaLR 0.01, Uncertain significance, Neurofibromatosis, type 1
- H4Y (p.His4Tyr), rs1911551060, ClinGen CA398979188, ClinVar RCV001934301, TOPMed rs1911551060, REVEL 0.08, MetaLR 0.02, Uncertain significance
- H4H (p.His4His), rs2143144553, gnomAD 17-31095321-C-T, CADD 19.70
- R5G (p.Arg5Gly), rs1598173775, ClinGen CA398979201, ClinVar RCV002006198, ClinVar RCV002388994, REVEL 0.07, MetaLR 0.02, Uncertain significance
- R5K (p.Arg5Lys), Ensembl rs2143144621, REVEL 0.06, AlphaMissense 0.91
- R5M (p.Arg5Met), Ensembl rs2143144621, REVEL 0.12, AlphaMissense 0.91
- R5S (p.Arg5Ser), rs1567786804, ClinGen CA398979213, ClinVar RCV000701041, ClinVar RCV002493226, REVEL 0.03, MetaLR 0.02, Uncertain significance
- R5T (p.Arg5Thr), rs2143144621, ClinGen CA398979205, ClinVar RCV003820000, AlphaMissense 0.91, MetaLR 0.01, Uncertain significance, Neurofibromatosis, type 1
- R5W (p.Arg5Trp), rs1598173775, ClinGen CA398979203, ClinVar RCV002319146, Ensembl rs1598173775, REVEL 0.09, MetaLR 0.02, Uncertain significance
- R5R (p.Arg5Arg), gnomAD 17-31095322-A-C, CADD 20.50
- P6L (p.Pro6Leu), rs864622210, ClinGen CA350124, ClinVar RCV000206070, ClinVar RCV002317732, REVEL 0.19, MetaLR 0.20, Uncertain significance
- P6Q (p.Pro6Gln), rs864622210, ClinGen CA398979222, ClinVar RCV002407869, REVEL 0.20, MetaLR 0.20, Uncertain significance
- P6R (p.Pro6Arg), rs864622210, ClinGen CA398979224, ClinVar RCV001776689, ClinVar RCV001885133, REVEL 0.22, MetaLR 0.20, Uncertain significance
- P6S (p.Pro6Ser), rs1567786812, ClinGen CA398979220, ClinVar RCV000757565, ClinVar RCV005092175, REVEL 0.16, MetaLR 0.18, Uncertain significance
- P6T (p.Pro6Thr), Ensembl rs1567786812, REVEL 0.16, MetaLR 0.18, Uncertain significance
- P6P (p.Pro6Pro), rs2143144771, gnomAD 17-31095327-G-T, CADD 20.50
- V7A (p.Val7Ala), gnomAD rs1472128030, REVEL 0.10, MetaLR 0.04, Uncertain significance, Neurofibromatosis, type 1
- V7D (p.Val7Asp), rs2143144854, ClinGen CA2573153207, ClinVar RCV001984738, Pathogenic
- V7G (p.Val7Gly), gnomAD rs1472128030, REVEL 0.14, MetaLR 0.03
- V7L (p.Val7Leu), Ensembl rs1911552278, REVEL 0.08, AlphaMissense 0.48, Uncertain significance
- V7M (p.Val7Met), rs1911552278, ClinGen CA398979228, ClinVar RCV001051473, ClinVar RCV004559867, AlphaMissense 0.48, MetaLR 0.05, Uncertain significance
- V7V (p.Val7Val), gnomAD 17-31095330-G-T, CADD 20.30
- E8* (p.Glu8Ter), cosmic curated COSV10466, NCI-TCGA TCGA novel, CADD 37.00, Variant assessed as somatic; high impact.
- E8D (p.Glu8Asp), rs2143144912, ClinGen CA2573153208, ClinVar RCV001972348, REVEL 0.12, MetaLR 0.08, Pathogenic
- E8G (p.Glu8Gly), Ensembl rs2143144904, MetaLR 0.08, MetaSVM -1.12
- E8K (p.Glu8Lys), gnomAD 17-31095331-G-A, REVEL 0.17, MetaLR 0.07
- E8V (p.Glu8Val), gnomAD 17-31095332-A-T, REVEL 0.18, MetaLR 0.08
- W9* (p.Trp9Ter), rs2143144971, ClinGen CA398979268, ClinVar RCV001982890, ClinVar RCV003222372, CADD 37.00, Pathogenic
- W9C (p.Trp9Cys), rs2143144971, ClinGen CA398979270, ClinVar RCV003599682, Ensembl rs2143144971, REVEL 0.42, MetaLR 0.19, Uncertain significance, Neurofibromatosis, type 1
- W9L (p.Trp9Leu), rs1567786829, ClinGen CA398979262, ClinVar RCV001337307, Ensembl rs1567786829, REVEL 0.24, MetaLR 0.18, Pathogenic
- W9R (p.Trp9Arg), rs1911552931, TOPMed rs1911552931, ClinGen CA398979258, ClinVar RCV003496935, REVEL 0.44, MetaLR 0.19, Uncertain significance, Neurofibromatosis, type 1
- V10A (p.Val10Ala), Ensembl rs2143145014, Uncertain significance
- V10D (p.Val10Asp), Ensembl rs2143145014, MetaLR 0.07, MetaSVM -1.13, Uncertain significance
- V10G (p.Val10Gly), rs2143145014, ClinGen CA398979281, ClinVar RCV003323125, Ensembl rs2143145014, REVEL 0.29, MetaLR 0.07, Uncertain significance, not provided
- V10I (p.Val10Ile), rs2544511291, ClinGen CA398979274, ClinVar RCV003495997, REVEL 0.09, MetaLR 0.05, Uncertain significance, Neurofibromatosis, type 1
- V10F (p.Val10Phe), gnomAD 17-31095337-G-T, REVEL 0.18, MetaLR 0.08
- V10V (p.Val10Val), rs1033348008, gnomAD 17-31095339-C-T, CADD 20.10
- Q11* (p.Gln11Ter), rs876658658, ClinGen CA10577556, ClinVar RCV000216917, ClinVar RCV000222237, CADD 36.00, Pathogenic
- Q11H (p.Gln11His), rs1431112645, gnomAD rs1431112645, ClinGen CA398979298, ClinVar RCV003497095, REVEL 0.11, MetaLR 0.06, Uncertain significance, Neurofibromatosis, type 1
- Q11L (p.Gln11Leu), Ensembl rs2143145095, REVEL 0.12, MetaLR 0.05, Uncertain significance, Cardiovascular phenotype; Hereditary cancer-predisposing syndrome
- Q11R (p.Gln11Arg), rs2143145095, ClinGen CA398979294, ClinVar RCV003597635, Ensembl rs2143145095, REVEL 0.12, MetaLR 0.05, Uncertain significance, Neurofibromatosis, type 1
- Q11K (p.Gln11Lys), gnomAD 17-31095340-C-A, REVEL 0.06, MetaLR 0.06
- Q11E (p.Gln11Glu), gnomAD 17-31095340-C-G, REVEL 0.05, MetaLR 0.05
- Q11Q (p.Gln11Gln), gnomAD 17-31095342-G-A, CADD 21.20
- A12G (p.Ala12Gly), Ensembl rs1911554964, MetaLR 0.06, MetaSVM -1.13, Uncertain significance
- A12T (p.Ala12Thr), rs2544511365, ClinGen CA398979303, ClinVar RCV003047619, ClinVar RCV005567367, REVEL 0.10, MetaLR 0.05, Uncertain significance
- A12V (p.Ala12Val), rs1911554964, ClinGen CA398979309, ClinVar RCV001203831, ClinVar RCV002451424, REVEL 0.10, MetaLR 0.05, Likely benign
- A12S (p.Ala12Ser), gnomAD 17-31095343-G-T, REVEL 0.09, MetaLR 0.04
- A12D (p.Ala12Asp), gnomAD 17-31095344-C-A, REVEL 0.25, MetaLR 0.06
- A12A (p.Ala12Ala), rs786203866, gnomAD 17-31095345-C-A, CADD 20.30
- V13A (p.Val13Ala), rs1911556061, ClinGen CA398979319, ClinVar RCV001036626, ClinVar RCV002298852, REVEL 0.22, MetaLR 0.03, Uncertain significance
- V13E (p.Val13Glu), Ensembl rs1911556061, Uncertain significance
- V13G (p.Val13Gly), Ensembl rs1911556061, MetaLR 0.05, MetaSVM -1.14, Uncertain significance
- V13L (p.Val13Leu), rs1060500261, ClinGen CA398979315, ClinVar RCV002319282, 1000Genomes rs1060500261, REVEL 0.12, MetaLR 0.01, Uncertain significance, Neurofibromatosis, type 1
- V13M (p.Val13Met), rs1060500261, ClinGen CA16615401, ClinVar RCV000461213, ClinVar RCV002365591, REVEL 0.12, MetaLR 0.06, Uncertain significance
- V13V (p.Val13Val), gnomAD 17-31095348-G-A, CADD 20.40
- V14A (p.Val14Ala), rs2143145332, ClinGen CA398979332, cosmic curated COSV10064, ClinVar RCV003032903, REVEL 0.21, AlphaMissense 0.80, Uncertain significance
- V14D (p.Val14Asp), rs2143145332, ClinGen CA398979334, ClinVar RCV003599831, ClinVar RCV004786997, AlphaMissense 0.80, MetaLR 0.02, Uncertain significance, Cardiovascular phenotype; Hereditary cancer-predisposing syndrome; not provided
- V14F (p.Val14Phe), rs2143145306, ClinGen CA398979327, ClinVar RCV002023004, ClinVar RCV002324487, REVEL 0.19, MetaLR 0.02, Uncertain significance
- V14G (p.Val14Gly), Ensembl rs2143145332, MetaLR 0.02, MetaSVM -1.03, Uncertain significance
- V14I (p.Val14Ile), gnomAD 17-31095349-G-A, REVEL 0.07, MetaLR 0.01
- V14V (p.Val14Val), rs755413799, gnomAD 17-31095351-C-A, CADD 20.20
- S15I (p.Ser15Ile), Ensembl rs1598173852, REVEL 0.07, MetaLR 0.02, Uncertain significance
- S15N (p.Ser15Asn), rs1598173852, ClinGen CA398979344, ClinVar RCV000815984, ClinVar RCV002319116, REVEL 0.05, MetaLR 0.01, Uncertain significance
- S15R (p.Ser15Arg), Ensembl rs2143145432, REVEL 0.09, MetaLR 0.02, Likely benign
- S15T (p.Ser15Thr), Ensembl rs1598173852, MetaLR 0.01, MetaSVM -0.95, Uncertain significance
- S15G (p.Ser15Gly), gnomAD 17-31095352-A-G, REVEL 0.04, MetaLR 0.02
- S15C (p.Ser15Cys), gnomAD 17-31095352-A-T, REVEL 0.10, MetaLR 0.03
- S15S (p.Ser15Ser), rs2143145432, gnomAD 17-31095354-C-T, CADD 20.50
- R16A (p.Arg16Ala), rs2544511498, ClinGen CA2573040366, ClinVar RCV002837707, Pathogenic
- R16C (p.Arg16Cys), rs1057520334, ClinGen CA16607554, ClinVar RCV000435513, ClinVar RCV000632423, REVEL 0.34, AlphaMissense 0.94, Uncertain significance
- R16G (p.Arg16Gly), rs1057520334, ClinGen CA398979366, ClinVar RCV003463159, ClinVar RCV004560186, AlphaMissense 0.94, MetaLR 0.11, Uncertain significance, Cardiovascular phenotype; Hereditary cancer-predisposing syndrome; Juvenile myel
- R16H (p.Arg16His), Ensembl rs1555594493, REVEL 0.25, AlphaMissense 1.00, Uncertain significance
- R16P (p.Arg16Pro), rs1555594493, ClinGen CA398979374, ClinVar RCV001212851, ClinVar RCV002316643, AlphaMissense 1.00, MetaLR 0.10, Uncertain significance
- R16S (p.Arg16Ser), gnomAD 17-31095355-C-A, REVEL 0.30, MetaLR 0.11
- R16L (p.Arg16Leu), gnomAD 17-31095356-G-T, REVEL 0.32, MetaLR 0.10
- R16R (p.Arg16Arg), gnomAD 17-31095357-C-A, CADD 20.20
- F17* (p.Phe17Ter), rs2544511554, ClinGen CA2580093206, ClinVar RCV002885113, Pathogenic
- F17C (p.Phe17Cys), rs1911557433, ClinGen CA398979388, ClinVar RCV001326500, Ensembl rs1911557433, AlphaMissense 0.99, MetaLR 0.09, Likely pathogenic
- F17I (p.Phe17Ile), Ensembl rs2143145538, MetaLR 0.09, MetaSVM -1.08
- F17L (p.Phe17Leu), rs1369290988, ClinGen CA398979393, ClinVar RCV000806661, gnomAD rs1369290988, REVEL 0.19, MetaLR 0.10, Uncertain significance
- F17S (p.Phe17Ser), rs1911557433, ClinGen CA398979385, ClinVar RCV002227922, ClinVar RCV002337412, REVEL 0.38, AlphaMissense 0.99, Likely pathogenic
- F17F (p.Phe17Phe), rs1369290988, gnomAD 17-31095360-C-T, CADD 20.40
- D18A (p.Asp18Ala), Ensembl rs2143145636, Uncertain significance
- D18E (p.Asp18Glu), TOPMed rs1598173882, REVEL 0.14, MetaLR 0.02, Likely benign
- D18G (p.Asp18Gly), rs2143145636, ClinGen CA398979403, ClinVar RCV002347248, Ensembl rs2143145636, REVEL 0.14, MetaLR 0.06, Uncertain significance
- D18H (p.Asp18His), Ensembl rs2143145613
- D18N (p.Asp18Asn), Ensembl rs2143145613, REVEL 0.10, MetaLR 0.06
- D18V (p.Asp18Val), Ensembl rs2143145636, MetaLR 0.07, MetaSVM -1.14, Uncertain significance
- D18Y (p.Asp18Tyr), gnomAD 17-31095361-G-T, REVEL 0.22, MetaLR 0.07
- D18D (p.Asp18Asp), rs1598173882, gnomAD 17-31095363-C-T, CADD 20.20
- E19* (p.Glu19Ter), rs786203307, ClinGen CA196174, ClinVar RCV000166554, ClinVar RCV000554192, CADD 37.00, Pathogenic
- E19A (p.Glu19Ala), rs1911558602, ClinGen CA398979418, ClinVar RCV001341497, Ensembl rs1911558602, AlphaMissense 0.36, MetaLR 0.06, Uncertain significance
- E19D (p.Glu19Asp), Ensembl rs2143145786, REVEL 0.08, MetaLR 0.04
- E19G (p.Glu19Gly), cosmic curated COSV99049, Ensembl rs1911558602, Uncertain significance
- E19K (p.Glu19Lys), rs786203307, ClinGen CA398979412, ClinVar RCV000706302, ClinVar RCV002343569, REVEL 0.10, MetaLR 0.05, Pathogenic
- E19V (p.Glu19Val), Ensembl rs1911558602, MetaLR 0.06, MetaSVM -1.16, Uncertain significance
- E19E (p.Glu19Glu), gnomAD 17-31095366-G-A, CADD 20.50
- Q20* (p.Gln20Ter), rs1567786905, ClinGen CA398979432, ClinVar RCV000698970, ClinVar RCV002352176, CADD 45.00, Pathogenic
- Q20E (p.Gln20Glu), rs1567786905, ClinGen CA398979430, ClinVar RCV001227828, ClinVar RCV002356968, REVEL 0.10, MetaLR 0.04, Pathogenic
- Q20H (p.Gln20His), rs1911559787, ClinGen CA398979442, ClinVar RCV003222909, ClinVar RCV003495327, REVEL 0.12, MetaLR 0.05, Uncertain significance, Neurofibromatosis, type 1; not provided
- Q20L (p.Gln20Leu), Ensembl rs1598173901, REVEL 0.11, AlphaMissense 0.58, Uncertain significance
- Q20P (p.Gln20Pro), rs1598173901, ClinGen CA398979435, ClinVar RCV000806247, ClinVar RCV005639213, AlphaMissense 0.58, MetaLR 0.03, Pathogenic
- Q20R (p.Gln20Arg), rs1598173901, ClinGen CA398979437, ClinVar RCV001372203, ClinVar RCV003169912, REVEL 0.11, AlphaMissense 0.58, Uncertain significance
- Q20K (p.Gln20Lys), gnomAD 17-31095367-C-A, REVEL 0.13, MetaLR 0.04
- L21F (p.Leu21Phe), ExAC rs779453629, gnomAD rs779453629, REVEL 0.22, AlphaMissense 0.85, Uncertain significance
- L21H (p.Leu21His), rs1567814403, ClinGen CA398988016, ClinVar RCV002038708, ClinVar RCV004558816, AlphaMissense 1.00, MetaLR 0.17, Uncertain significance
- L21I (p.Leu21Ile), rs779453629, ClinGen CA398988008, ClinVar RCV002366443, ExAC rs779453629, AlphaMissense 0.85, MetaLR 0.18, Uncertain significance
- L21P (p.Leu21Pro), rs1567814403, ClinGen CA398988021, cosmic curated COSV62207, ClinVar RCV000700381, AlphaMissense 1.00, MetaLR 0.17, Uncertain significance
- L21V (p.Leu21Val), rs779453629, ClinGen CA398988010, ClinVar RCV001306574, ExAC rs779453629, AlphaMissense 0.85, MetaLR 0.18, Uncertain significance
- P22A (p.Pro22Ala), rs1597625794, ClinGen CA398988026, ClinVar RCV001038649, Ensembl rs1597625794, REVEL 0.41, MetaLR 0.11, Uncertain significance
- P22L (p.Pro22Leu), rs2065654347, ClinGen CA398988047, ClinVar RCV001230396, ClinVar RCV003317460, AlphaMissense 0.92, MetaLR 0.11, Uncertain significance
- P22S (p.Pro22Ser), rs1597625794, ClinGen CA398988030, cosmic curated COSV62206, ClinVar RCV000989777, REVEL 0.41, MetaLR 0.11, Uncertain significance
- P22T (p.Pro22Thr), Ensembl rs1597625794, REVEL 0.44, MetaLR 0.11, Uncertain significance
- P22N (p.Pro22Asn), gnomAD 17-31155985-TCC-T, CADD 27.20
- p.Pro22 Ile23insPheLeu, gnomAD 17-31155987-C-CTT, CADD 18.80
- I23* (p.Ile23Ter), rs1597625799, ClinGen CA915949690, ClinVar RCV001008734, Pathogenic
- I23L (p.Ile23Leu), cosmic curated COSV62197, 1000Genomes rs542824372, ExAC rs542824372, TOPMed rs542824372, MetaLR 0.06, MetaSVM -1.13, Benign
- I23M (p.Ile23Met), rs1555604870, ClinGen CA398988068, ClinVar RCV002316651, ClinVar RCV002528015, REVEL 0.13, MetaLR 0.05, Uncertain significance
- I23V (p.Ile23Val), rs542824372, ClinGen CA8485473, ClinVar RCV000460803, ClinVar RCV001797086, REVEL 0.16, MetaLR 0.04, Benign
- K24* (p.Lys24Ter), rs2143625250, ClinGen CA398988072, ClinVar RCV001889108, Ensembl rs2143625250, Pathogenic
- K24N (p.Lys24Asn), rs2143625276, ClinVar RCV004560808, Ensembl rs2143625276, AlphaMissense 0.91, MetaLR 0.03, Uncertain significance, Hereditary cancer-predisposing syndrome; Cardiovascular phenotype
- K24R (p.Lys24Arg), rs2143625259, ClinGen CA398988078, ClinVar RCV002370831, Ensembl rs2143625259, AlphaMissense 0.08, MetaLR 0.02, Uncertain significance
- T25A (p.Thr25Ala), Ensembl rs2143625282
- T25I (p.Thr25Ile), rs1555604874, ClinGen CA398988104, ClinVar RCV000573262, ClinVar RCV001067528, REVEL 0.09, AlphaMissense 0.12, Uncertain significance, not specified
- T25N (p.Thr25Asn), rs2143625205, ClinGen CA2573153516, ClinVar RCV002037851, ClinVar RCV002361296, Pathogenic
- T25P (p.Thr25Pro), Ensembl rs2143625282, Uncertain significance, Cardiovascular phenotype; Hereditary cancer-predisposing syndrome
- T25Q (p.Thr25Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T25R (p.Thr25Arg), rs1555604874, ClinGen CA398988102, ClinVar RCV001049539, Ensembl rs1555604874, AlphaMissense 0.12, MetaLR 0.02, Uncertain significance
- T25S (p.Thr25Ser), Ensembl rs2143625282, MetaLR 0.03, MetaSVM -1.09
- T25K (p.Thr25Lys), gnomAD 17-31155996-C-A, REVEL 0.10, MetaLR 0.03
- G26A (p.Gly26Ala), Ensembl rs2143625375, Uncertain significance
- G26D (p.Gly26Asp), rs2143625360, ClinGen CA2573153519, ClinVar RCV001916555, Pathogenic
- G26E (p.Gly26Glu), rs2143625375, ClinGen CA398988113, ClinVar RCV001928932, Ensembl rs2143625375, AlphaMissense 0.35, MetaLR 0.06, Uncertain significance
- G26R (p.Gly26Arg), rs778973022, ExAC rs778973022, gnomAD rs778973022, ClinGen CA8485475, REVEL 0.15, MetaLR 0.05, Uncertain significance
- G26V (p.Gly26Val), Ensembl rs2143625375, MetaLR 0.05, MetaSVM -1.10, Uncertain significance
- G26G (p.Gly26Gly), rs748018099, gnomAD 17-31156000-A-T, CADD 12.90
- Q27* (p.Gln27Ter), rs1060500363, ClinGen CA16615539, ClinVar RCV000469252, ClinVar RCV000585221, Pathogenic
- Q27H (p.Gln27His), Ensembl rs1597625846, MetaLR 0.01, MetaSVM -0.96, Likely benign
- Q27Q (p.Gln27Gln), rs1597625846, gnomAD 17-31156003-G-A, CADD 3.99
- Q28* (p.Gln28Ter), rs771764281, ClinGen CA398988142, cosmic curated COSV62194, ClinVar RCV000492657, AlphaMissense 0.11, MetaLR 0.03, Pathogenic
- Q28E (p.Gln28Glu), ExAC rs771764281, gnomAD rs771764281, REVEL 0.17, AlphaMissense 0.11, Pathogenic
- Q28H (p.Gln28His), Ensembl rs2143625465, MetaLR 0.04, MetaSVM -1.08
- Q28P (p.Gln28Pro), rs587782686, ClinGen CA169288, ClinVar RCV000132116, ClinVar RCV000203778, REVEL 0.35, MetaLR 0.06, Uncertain significance
- N29K (p.Asn29Lys), rs1060503914, ClinGen CA398988167, ClinVar RCV003047879, TOPMed rs1060503914, AlphaMissense 0.42, MetaLR 0.02, Uncertain significance, Neurofibromatosis, type 1
- N29S (p.Asn29Ser), rs2544680852, ClinGen CA398988165, ClinVar RCV003041493, ClinVar RCV005375244, Likely benign
- T30A (p.Thr30Ala), rs1555604881, ClinGen CA398988174, ClinVar RCV003228448, ClinVar RCV003598165, AlphaMissense 0.09, MetaLR 0.06, Uncertain significance, Cardiovascular phenotype; Hereditary cancer-predisposing syndrome; not provided
- T30I (p.Thr30Ile), Ensembl rs2143625564, REVEL 0.33, MetaLR 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Cardiovascular phenotype
- T30K (p.Thr30Lys), Ensembl rs2143625564, Uncertain significance
- T30P (p.Thr30Pro), rs1555604881, ClinGen CA398988172, ClinVar RCV000550449, ClinVar RCV001764536, AlphaMissense 0.09, MetaLR 0.06, Uncertain significance
- T30R (p.Thr30Arg), Ensembl rs2143625564, REVEL 0.37, MetaLR 0.09, Uncertain significance
- T30S (p.Thr30Ser), Ensembl rs1555604881, MetaLR 0.09, MetaSVM -1.09, Uncertain significance
- T30T (p.Thr30Thr), rs1336406332, gnomAD 17-31156012-A-G, CADD 7.44
- H31D (p.His31Asp), rs786202864, ClinGen CA398988181, ClinVar RCV001046801, gnomAD rs786202864, AlphaMissense 0.36, MetaLR 0.09, Likely benign, in NF1
- H31P (p.His31Pro), rs199474725, ClinGen CA398988185, ClinVar RCV002371510, ClinVar RCV004572395, AlphaMissense 0.24, MetaLR 0.08, Uncertain significance, in NF1
- H31Q (p.His31Gln), rs2143625630, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Ensembl rs2143625630, AlphaMissense 0.25, MetaLR 0.03, Uncertain significance, Neurofibromatosis, type 1
- H31R (p.His31Arg), rs199474725, ClinGen CA219643, ClinVar RCV000059218, ClinVar RCV001854237, REVEL 0.46, AlphaMissense 0.24, Pathogenic, in NF1
Public NF1 analysis runs
- NF1 analysis run — NF1 (13,101 variants) — completed 2026-08-18