TMEM127 (Transmembrane protein 127) variants and mutations
TMEM127 (also known as Transmembrane protein 127) is a human protein-coding gene encoding a transmembrane protein 127 protein. It restrains growth signaling and participates in endomembrane trafficking, including regulation of mTOR-related pathways. Germline loss-of-function variants predispose primarily to pheochromocytoma and paraganglioma and can also occur in selected renal tumors. This analysis covers 1,049 TMEM127 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes pheochromocytoma, hereditary pheochromocytoma-paraganglioma, and hereditary neoplastic syndrome. Example TMEM127 variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: TMEM127
- Protein: Transmembrane protein 127
- UniProt accession: O75204
- Organism: Homo sapiens
- Variants analyzed: 1049
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 781 unspecified-consequence records; 151 synonymous variants; 83 missense variants; 18 frameshift variants; 7 stop-gained variants; 1 in-frame insertions; 3 in-frame deletions; 3 splice-region variants; 4 substitution
- Prediction scores: 833 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pheochromocytoma, hereditary pheochromocytoma-paraganglioma, hereditary neoplastic syndrome, Inherited cancer-predisposing syndrome, malignant endocrine neoplasm, melanoma, carcinoma of liver and intrahepatic biliary tract, intestinal neuroendocrine tumor G1, Cowden syndrome 3, pheochromocytoma/paraganglioma syndrome 1, Cowden disease, Carney-Stratakis syndrome.
Protein structure and variant hotspots
- Protein features: 3 transmembrane segments; 2 post-translational modification sites.
- Structural context: 249 variants have structural context.
- PTM context: 11 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 TMEM127 variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, Y2C, Y2D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs121908814, ClinGen CA269750, ClinVar RCV000114827, ClinVar RCV000566096, MetaLR 0.81, MetaSVM 0.43, Pathogenic, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- M1K (p.Met1Lys), rs1684398953, ClinGen CA347656376, ClinVar RCV001999957, ClinVar RCV006287556, MetaLR 0.80, MetaSVM 0.49, Pathogenic, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- M1L (p.Met1Leu), rs1553437759, ClinGen CA347656381, ClinVar RCV001221200, ClinVar RCV005749753, MetaLR 0.77, MetaSVM 0.37, Pathogenic, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- M1R (p.Met1Arg), rs1684398953, ClinGen CA347656379, ClinVar RCV001062786, ClinVar RCV002436648, MetaLR 0.80, MetaSVM 0.49, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- M1T (p.Met1Thr), rs1684398953, ClinGen CA347656377, ClinVar RCV003485907, ClinVar RCV004333281, MetaLR 0.80, MetaSVM 0.49, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- M1V (p.Met1Val), rs1553437759, ClinGen CA347656382, ClinVar RCV000579097, MetaLR 0.77, MetaSVM 0.37, Uncertain significance, not provided
- Y2C (p.Tyr2Cys), rs1368865164, ClinGen CA347656363, ClinVar RCV001024780, ClinVar RCV001352296, REVEL 0.56, CADD 31.00, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- Y2D (p.Tyr2Asp), rs2104308652, ClinGen CA347656366, ClinVar RCV002343066, ClinVar RCV003102671, AlphaMissense 0.50, MetaLR 0.82, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- Y2H (p.Tyr2His), rs2104308652, ClinGen CA347656368, ClinVar RCV001368963, Ensembl rs2104308652, REVEL 0.50, AlphaMissense 0.50, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- Y2Y (p.Tyr2Tyr), rs2104308630, gnomAD 2-96265376-G-A, CADD 13.00
- Y2* (p.Tyr2Ter), gnomAD 2-96265376-G-T, CADD 35.00
- A3D (p.Ala3Asp), rs1553437754, ClinGen CA347656350, ClinVar RCV004522263, REVEL 0.32, AlphaMissense 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome
- A3G (p.Ala3Gly), rs1553437754, ClinGen CA347656349, ClinVar RCV002376341, ClinVar RCV003103550, AlphaMissense 0.16, MetaLR 0.77, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A3T (p.Ala3Thr), Ensembl rs2104308614, REVEL 0.30, CADD 23.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- A3V (p.Ala3Val), rs1553437754, ClinGen CA347656347, ClinVar RCV000538248, ClinVar RCV005286116, REVEL 0.37, AlphaMissense 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A3A (p.Ala3Ala), gnomAD 2-96265373-G-A, CADD 16.50
- A3S (p.Ala3Ser), gnomAD 2-96265375-C-A, REVEL 0.33, MetaLR 0.71
- P4L (p.Pro4Leu), cosmic curated COSV51498, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P4S (p.Pro4Ser), rs1024081498, ClinGen CA52419186, ClinVar RCV000639346, ClinVar RCV001017295, REVEL 0.44, AlphaMissense 0.07, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- P4T (p.Pro4Thr), rs1024081498, ClinGen CA347656346, ClinVar RCV002430813, AlphaMissense 0.07, MetaLR 0.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- P4P (p.Pro4Pro), gnomAD 2-96265370-G-T, CADD 12.20
- G5* (p.Gly5Ter), rs786202314, ClinGen CA347656335, ClinVar RCV003828082, CADD 36.00, Pathogenic
- G5E (p.Gly5Glu), rs1684396954, ClinGen CA347656332, ClinVar RCV003635403, NCI-TCGA TCGA novel, REVEL 0.24, CADD 23.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- G5R (p.Gly5Arg), rs786202314, ClinGen CA192410, ClinVar RCV000165058, ClinVar RCV001301455, REVEL 0.25, CADD 24.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- G5G (p.Gly5Gly), rs2104308562, gnomAD 2-96265367-T-C, CADD 17.60
- G6S (p.Gly6Ser), rs2467286325, ClinGen CA347656329, ClinVar RCV003634907, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- G6V (p.Gly6Val), rs2467286322, ClinGen CA347656322, ClinVar RCV003104191, ClinVar RCV004572845, REVEL 0.56, CADD 23.90, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Pheochromocytoma
- G6D (p.Gly6Asp), gnomAD 2-96265365-C-T, REVEL 0.53, CADD 26.50
- G6C (p.Gly6Cys), gnomAD 2-96265366-C-A, REVEL 0.55, CADD 28.50
- G6R (p.Gly6Arg), gnomAD 2-96265366-C-G, REVEL 0.56, MetaLR 0.87
- A7G (p.Ala7Gly), rs1357430519, ClinGen CA347656313, ClinVar RCV002000746, TOPMed rs1357430519, AlphaMissense 0.10, MetaLR 0.70, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A7S (p.Ala7Ser), rs1390402715, ClinGen CA347656320, ClinVar RCV002417098, ClinVar RCV003108096, REVEL 0.24, CADD 16.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A7T (p.Ala7Thr), rs1390402715, ClinGen CA347656317, ClinVar RCV000639358, ClinVar RCV003162867, REVEL 0.27, CADD 18.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A7V (p.Ala7Val), rs1357430519, ClinGen CA347656312, ClinVar RCV001346570, TOPMed rs1357430519, REVEL 0.34, AlphaMissense 0.10, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A7R (p.Ala7Arg), rs1684396835, gnomAD 2-96265361-TGC-T, CADD 32.00
- A7A (p.Ala7Ala), rs2104308513, gnomAD 2-96265361-T-C, CADD 17.00
- G8V (p.Gly8Val), rs1573978044, ClinGen CA347656301, ClinVar RCV001015413, ClinVar RCV003633553, REVEL 0.28, CADD 22.90, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- G8G (p.Gly8Gly), gnomAD 2-96265358-C-T, CADD 15.70
- G8W (p.Gly8Trp), gnomAD 2-96265360-C-A, REVEL 0.46, CADD 24.90
- L9P (p.Leu9Pro), Ensembl rs2104308474, REVEL 0.50, AlphaMissense 0.09, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- L9R (p.Leu9Arg), rs2104308474, ClinGen CA347656294, ClinVar RCV003288252, AlphaMissense 0.09, MetaLR 0.67, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- p.Leu9 Gly11del, rs1684396239, gnomAD 2-96265349-GCCGGG, CADD 22.40
- L9L (p.Leu9Leu), gnomAD 2-96265355-C-A, CADD 14.90
- P10L (p.Pro10Leu), cosmic curated COSV10506, REVEL 0.40, CADD 25.20, Uncertain significance, Pheochromocytoma
- P10S (p.Pro10Ser), rs1161858061, ClinGen CA347656289, ClinVar RCV001210301, ClinVar RCV006287354, REVEL 0.32, CADD 22.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P10P (p.Pro10Pro), rs963234474, gnomAD 2-96265352-G-A, CADD 15.60
- G11A (p.Gly11Ala), ExAC rs773493345, gnomAD rs773493345, REVEL 0.33, AlphaMissense 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome
- G11C (p.Gly11Cys), rs992633976, ClinGen CA52419168, ClinVar RCV000700061, ClinVar RCV000761105, REVEL 0.43, CADD 23.00, Uncertain significance, Acute promyelocytic leukemia; Hereditary pheochromocytoma and paraganglioma; Her
- G11D (p.Gly11Asp), rs773493345, ClinGen CA347656278, ClinVar RCV001918881, ExAC rs773493345, AlphaMissense 0.33, MetaLR 0.65, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- G11R (p.Gly11Arg), TOPMed rs992633976, gnomAD rs992633976, Uncertain significance
- G11S (p.Gly11Ser), rs992633976, ClinGen CA347656282, ClinVar RCV002721897, TOPMed rs992633976, REVEL 0.22, CADD 19.90, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- G11G (p.Gly11Gly), rs1268280072, gnomAD 2-96265349-G-A, CADD 15.30
- G11V (p.Gly11Val), gnomAD 2-96265350-C-A, REVEL 0.38, CADD 22.70
- G12A (p.Gly12Ala), Ensembl rs2104308408, MetaLR 0.58, MetaSVM -0.12, Uncertain significance
- G12E (p.Gly12Glu), rs2104308408, ClinGen CA347656270, ClinVar RCV002455188, ClinVar RCV005096329, REVEL 0.37, CADD 21.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- G12R (p.Gly12Arg), rs1684396039, ClinGen CA347656275, ClinVar RCV001953171, ClinVar RCV004681346, REVEL 0.27, CADD 22.60, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- R13C (p.Arg13Cys), rs1684395977, ClinGen CA347656263, ClinVar RCV002355167, ClinVar RCV003475343, REVEL 0.31, CADD 24.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Hereditary pheochromo
- R13P (p.Arg13Pro), Ensembl rs2104308397, MetaLR 0.70, MetaSVM 0.16
- R13R (p.Arg13Arg), rs1060503975, gnomAD 2-96265343-G-T, CADD 16.00
- R13L (p.Arg13Leu), gnomAD 2-96265344-C-A, REVEL 0.36, CADD 23.30
- R13H (p.Arg13His), gnomAD 2-96265344-C-T, REVEL 0.44, CADD 23.60
- R13S (p.Arg13Ser), gnomAD 2-96265345-G-T, REVEL 0.31, CADD 22.80
- R14G (p.Arg14Gly), rs1684395815, ClinGen CA347656256, ClinVar RCV001940832, ClinVar RCV003167351, AlphaMissense 0.14, MetaLR 0.33, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- R14Q (p.Arg14Gln), rs2104308364, ClinGen CA347656253, ClinVar RCV003216542, Ensembl rs2104308364, REVEL 0.26, CADD 23.90, Uncertain significance, Hereditary cancer-predisposing syndrome
- R14W (p.Arg14Trp), rs1684395815, ClinGen CA347656255, ClinVar RCV003634339, gnomAD rs1684395815, REVEL 0.47, AlphaMissense 0.14, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- R14R (p.Arg14Arg), gnomAD 2-96265340-C-T, CADD 16.30
- R14L (p.Arg14Leu), gnomAD 2-96265341-C-A, REVEL 0.49, CADD 25.40
- R15G (p.Arg15Gly), rs1684395770, ClinGen CA347656249, ClinVar RCV003834213, ClinVar RCV005752306, REVEL 0.51, CADD 23.80, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- R15L (p.Arg15Leu), rs2104308338, ClinGen CA347656242, ClinVar RCV001977883, ClinVar RCV003464345, REVEL 0.43, CADD 24.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Pheochromocytoma
- R15Q (p.Arg15Gln), rs2104308338, ClinGen CA347656245, ClinVar RCV002654956, REVEL 0.34, CADD 23.90, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- R15W (p.Arg15Trp), rs1684395770, ClinGen CA347656247, ClinVar RCV002333723, REVEL 0.61, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- R15R (p.Arg15Arg), gnomAD 2-96265337-C-A, CADD 16.30
- R16G (p.Arg16Gly), rs767737615, ClinGen CA1777406, ClinVar RCV001931328, ClinVar RCV002331475, REVEL 0.49, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- R16K (p.Arg16Lys), rs1245811763, ClinGen CA347656235, ClinVar RCV002330736, TOPMed rs1245811763, REVEL 0.34, CADD 25.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- R16S (p.Arg16Ser), rs2104308307, ClinGen CA347656232, ClinVar RCV003634559, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S17G (p.Ser17Gly), rs1249001227, ClinGen CA347656228, ClinVar RCV001053544, ClinVar RCV002339269, REVEL 0.33, CADD 22.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Hereditary pheochromo
- S17I (p.Ser17Ile), rs1223613323, ClinGen CA347656221, ClinVar RCV000812977, ClinVar RCV003166321, REVEL 0.18, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Hereditary pheochromo
- S17N (p.Ser17Asn), gnomAD rs1223613323, REVEL 0.21, CADD 21.60, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S17R (p.Ser17Arg), rs2467286026, ClinGen CA347656218, ClinVar RCV003301479, Uncertain significance, Hereditary cancer-predisposing syndrome
- S17S (p.Ser17Ser), gnomAD 2-96265331-G-A, CADD 14.30
- P18L (p.Pro18Leu), rs377740271, ClinGen CA1777405, cosmic curated COSV99302, ClinVar RCV000231126, REVEL 0.19, CADD 23.00, Benign/Likely benign, Multiple mitochondrial dysfunctions syndrome 10; Hereditary pheochromocytoma and
- P18R (p.Pro18Arg), rs377740271, ClinGen CA347656212, ClinVar RCV003516687, 1000Genomes rs377740271, REVEL 0.22, CADD 21.90, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- P18S (p.Pro18Ser), rs1452142786, ClinGen CA16621984, ClinVar RCV000566858, ClinVar RCV000639357, REVEL 0.24, CADD 22.90, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; not provided
- P18P (p.Pro18Pro), gnomAD 2-96265328-C-T, CADD 13.90
- P18T (p.Pro18Thr), gnomAD 2-96265330-G-T, REVEL 0.24, CADD 22.80
- G19* (p.Gly19Ter), rs774322340, ClinGen CA347656206, ClinVar RCV003219129, ClinVar RCV005505637, CADD 35.00, Pathogenic
- G19R (p.Gly19Arg), rs774322340, ClinGen CA347656208, ClinVar RCV001294735, ClinVar RCV002350509, REVEL 0.18, CADD 22.60, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- G19V (p.Gly19Val), rs1331019402, ClinGen CA347656203, ClinVar RCV000525022, ClinVar RCV002350259, REVEL 0.24, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- G19E (p.Gly19Glu), gnomAD 2-96265325-TC-T, CADD 25.90
- G19G (p.Gly19Gly), rs1269002433, gnomAD 2-96265325-T-G, CADD 15.80
- G20D (p.Gly20Asp), gnomAD rs1295676044, REVEL 0.20, CADD 22.80, Uncertain significance
- G20S (p.Gly20Ser), rs1343615968, ClinGen CA347656202, ClinVar RCV001344508, ClinVar RCV003478789, REVEL 0.21, CADD 22.00, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyto
- G20V (p.Gly20Val), gnomAD rs1295676044, MetaLR 0.26, MetaSVM -0.74, Uncertain significance, Pheochromocytoma
- G20G (p.Gly20Gly), rs768746694, gnomAD 2-96265322-G-A, CADD 16.00
- S21C (p.Ser21Cys), rs2467285981, ClinGen CA347656194, ClinVar RCV003466447, ClinVar RCV006473253, REVEL 0.29, CADD 23.60, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Pheochromocytoma
- S21N (p.Ser21Asn), rs1348645128, ClinGen CA347656193, ClinVar RCV000563807, ClinVar RCV000706462, REVEL 0.26, CADD 20.50, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- S21R (p.Ser21Arg), rs1573977946, Ensembl rs1573977946, ClinGen CA347656189, ClinVar RCV001201544, AlphaMissense 0.43, MetaLR 0.22, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S21S (p.Ser21Ser), rs1573977946, gnomAD 2-96265319-G-A, AlphaMissense 0.43, MetaLR 0.22
- A22G (p.Ala22Gly), rs1573977937, ClinGen CA347656184, ClinVar RCV003633872, AlphaMissense 0.10, MetaLR 0.33, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A22P (p.Ala22Pro), rs1273425757, ClinGen CA347656186, ClinVar RCV002364135, AlphaMissense 0.09, MetaLR 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome
- A22T (p.Ala22Thr), rs1273425757, ClinGen CA347656187, ClinVar RCV000697252, ClinVar RCV003303154, REVEL 0.21, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome; Pheochromocytoma; Hereditary pheochromo
- A22V (p.Ala22Val), rs1573977937, ClinGen CA347656183, ClinVar RCV001025443, ClinVar RCV002552399, REVEL 0.29, AlphaMissense 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A22S (p.Ala22Ser), gnomAD 2-96265318-C-A, REVEL 0.21, CADD 18.90
- L23M (p.Leu23Met), rs749807415, ClinGen CA347656182, ClinVar RCV000554350, ClinVar RCV001294226, REVEL 0.31, CADD 24.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- L23L (p.Leu23Leu), rs2104308188, gnomAD 2-96265313-C-T, AlphaMissense 0.09, MetaLR 0.14
- P24R (p.Pro24Arg), rs1231130879, ClinGen CA347656173, ClinVar RCV000639353, ClinVar RCV002369667, REVEL 0.67, AlphaMissense 0.16, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- P24S (p.Pro24Ser), Ensembl rs2104308180, REVEL 0.47, CADD 24.80, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- P24P (p.Pro24Pro), gnomAD 2-96265310-G-T, AlphaMissense 0.27, MetaLR 0.09
- P24L (p.Pro24Leu), gnomAD 2-96265311-G-A, REVEL 0.47, AlphaMissense 0.39
- P24H (p.Pro24His), gnomAD 2-96265311-G-T, REVEL 0.58, AlphaMissense 0.31
- K25* (p.Lys25Ter), rs1573977924, ClinGen CA347656169, ClinVar RCV001026387, ClinVar RCV002551958, CADD 37.00, Pathogenic
- K25N (p.Lys25Asn), rs1573977916, ClinGen CA347656165, ClinVar RCV001026611, TOPMed rs1573977916, REVEL 0.51, CADD 26.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- K25R (p.Lys25Arg), rs2467285908, ClinGen CA347656167, ClinVar RCV003227182, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- K25S (p.Lys25Ser), rs1223474344, gnomAD 2-96265307-CT-C, CADD 29.30
- K25K (p.Lys25Lys), rs1573977916, gnomAD 2-96265307-C-T, CADD 15.00
- Q26* (p.Gln26Ter), rs121908815, ClinGen CA269764, ClinVar RCV000114835, ClinVar RCV003517136, CADD 37.00, Pathogenic
- Q26H (p.Gln26His), rs2467285886, ClinGen CA347656157, ClinVar RCV003635164, REVEL 0.47, CADD 24.10, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- Q26R (p.Gln26Arg), cosmic curated COSV51496, REVEL 0.43, CADD 24.00, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- Q26Q (p.Gln26Gln), gnomAD 2-96265304-C-T, CADD 14.60
- Q26K (p.Gln26Lys), gnomAD 2-96265306-G-T, REVEL 0.41, CADD 23.20
- P27L (p.Pro27Leu), rs983504110, ClinGen CA16611042, ClinVar RCV000472779, ClinVar RCV002418353, REVEL 0.40, CADD 23.70, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- P27R (p.Pro27Arg), rs983504110, ClinGen CA347656152, ClinVar RCV001895422, ClinVar RCV004041234, REVEL 0.47, CADD 22.90, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary pheochromocyto
- P27S (p.Pro27Ser), rs2104308146, ClinGen CA347656154, ClinVar RCV003060201, ClinVar RCV004676119, REVEL 0.34, CADD 23.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- P27P (p.Pro27Pro), rs1553437743, gnomAD 2-96265301-C-G, CADD 12.70
- P27Q (p.Pro27Gln), gnomAD 2-96265302-G-T, REVEL 0.43, CADD 24.90
- P27T (p.Pro27Thr), gnomAD 2-96265303-G-T, REVEL 0.42, CADD 23.00
- E28* (p.Glu28Ter), rs776127077, ClinGen CA1777401, ClinVar RCV002736802, ExAC rs776127077, AlphaMissense 0.92, MetaLR 0.23, Pathogenic
- E28G (p.Glu28Gly), Ensembl rs2104308114, MetaLR 0.53, MetaSVM 0.15
- E28E (p.Glu28Glu), gnomAD 2-96265298-C-T, CADD 14.70
- E28D (p.Glu28Asp), gnomAD 2-96265298-C-A, REVEL 0.65, CADD 25.50
- R29C (p.Arg29Cys), Ensembl rs2104308107
- R29H (p.Arg29His), rs1649983150, ClinGen CA347656141, ClinVar RCV002373417, ClinVar RCV003100003, REVEL 0.66, AlphaMissense 0.59, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- R29L (p.Arg29Leu), TOPMed rs1649983150, REVEL 0.71, AlphaMissense 0.82
- R29S (p.Arg29Ser), rs2104308107, ClinGen CA347656144, ClinVar RCV004522262, REVEL 0.55, CADD 25.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- R29R (p.Arg29Arg), rs1477658265, gnomAD 2-96265295-A-G, CADD 14.70
- S30G (p.Ser30Gly), rs763476625, ClinGen CA16611134, ClinVar RCV000466113, ClinVar RCV000572003, REVEL 0.48, CADD 26.90, Conflicting interpretations, not provided; Hereditary cancer-predisposing syndrome; Hereditary pheochromocyto
- S30I (p.Ser30Ile), rs2104308085, ClinGen CA347656134, ClinVar RCV002011661, Ensembl rs2104308085, REVEL 0.62, AlphaMissense 0.98, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S30N (p.Ser30Asn), rs2104308085, ClinGen CA347656136, ClinVar RCV002805432, AlphaMissense 0.98, MetaLR 0.50, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- S30R (p.Ser30Arg), TOPMed rs763476625, gnomAD rs763476625, REVEL 0.63, CADD 25.20, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- S30S (p.Ser30Ser), gnomAD 2-96265292-G-A, CADD 14.80
- L31P (p.Leu31Pro), rs2467285819, ClinGen CA347656128, ClinVar RCV002371539, ClinVar RCV005097326, REVEL 0.75, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- L31L (p.Leu31Leu), gnomAD 2-96265289-C-T, CADD 14.80
- L31M (p.Leu31Met), gnomAD 2-96265291-G-T, REVEL 0.50, CADD 27.90
- A32P (p.Ala32Pro), rs770347064, ClinGen CA347656125, ClinVar RCV002374138, AlphaMissense 0.45, MetaLR 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome
- A32S (p.Ala32Ser), rs770347064, ClinGen CA1777400, ClinVar RCV000553017, ClinVar RCV002377064, REVEL 0.36, AlphaMissense 0.45, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A32T (p.Ala32Thr), rs770347064, ClinGen CA347656126, ClinVar RCV001362729, ExAC rs770347064, REVEL 0.35, AlphaMissense 0.45, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A32V (p.Ala32Val), rs1459156138, ClinGen CA347656122, ClinVar RCV000639350, gnomAD rs1459156138, REVEL 0.21, CADD 22.00, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A32A (p.Ala32Ala), gnomAD 2-96265286-G-A, CADD 14.30
- A32D (p.Ala32Asp), gnomAD 2-96265287-G-T, REVEL 0.58, CADD 27.40
- S33L (p.Ser33Leu), rs1573977887, ClinGen CA347656116, cosmic curated COSV51498, ClinVar RCV001019874, REVEL 0.73, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- S33S (p.Ser33Ser), rs746237736, gnomAD 2-96265283-C-A, CADD 14.20
- S33* (p.Ser33Ter), gnomAD 2-96265284-G-T, CADD 37.00
- A34D (p.Ala34Asp), rs1451389209, ClinGen CA347656112, ClinVar RCV000707080, TOPMed rs1451389209, REVEL 0.69, CADD 32.00, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A34G (p.Ala34Gly), rs1451389209, ClinGen CA347656111, ClinVar RCV001009719, ClinVar RCV001369094, REVEL 0.57, CADD 31.00, Uncertain significance, Hereditary pheochromocytoma and paraganglioma; Hereditary cancer-predisposing sy
- A34T (p.Ala34Thr), rs1553437740, ClinGen CA347656115, ClinVar RCV000536078, ClinVar RCV002438352, AlphaMissense 0.98, MetaLR 0.55, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A34V (p.Ala34Val), rs1451389209, ClinGen CA347656110, ClinVar RCV001009722, TOPMed rs1451389209, REVEL 0.63, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- A34A (p.Ala34Ala), rs781643869, gnomAD 2-96265280-G-A, CADD 14.10
- A34S (p.Ala34Ser), gnomAD 2-96265282-C-A, REVEL 0.59, CADD 24.40
- L35P (p.Leu35Pro), rs2467285775, ClinGen CA347656106, ClinVar RCV003104651, ClinVar RCV004949029, REVEL 0.77, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- L35L (p.Leu35Leu), rs2104308019, gnomAD 2-96265277-C-T, CADD 13.60
- L35C (p.Leu35Cys), gnomAD 2-96265278-AG-A, CADD 24.30
- L35Q (p.Leu35Gln), gnomAD 2-96265278-A-T, REVEL 0.72, CADD 31.00
- L35M (p.Leu35Met), gnomAD 2-96265279-G-T, REVEL 0.52, CADD 23.00
- P36L (p.Pro36Leu), rs2104308005, ClinGen CA347656099, ClinVar RCV003320962, Ensembl rs2104308005, AlphaMissense 0.71, MetaLR 0.25, Uncertain significance, not specified
- P36S (p.Pro36Ser), rs2104308011, ClinGen CA347656104, ClinVar RCV003181667, ClinVar RCV003633686, AlphaMissense 0.92, MetaLR 0.44, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- p.Pro36 Leu39del, gnomAD 2-96265264-ACAGGG, CADD 22.50
- P36P (p.Pro36Pro), gnomAD 2-96265274-A-T, CADD 13.90
- P36H (p.Pro36His), gnomAD 2-96265275-G-T, REVEL 0.69, CADD 29.40
- P36T (p.Pro36Thr), gnomAD 2-96265276-G-T, REVEL 0.63, CADD 24.90
- G37A (p.Gly37Ala), gnomAD rs1684393209, MetaLR 0.37, MetaSVM -0.39, Uncertain significance
- G37D (p.Gly37Asp), rs1684393209, ClinGen CA347656093, ClinVar RCV003149192, ClinVar RCV003164869, REVEL 0.71, CADD 27.70, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Pheochromocytoma
- G37V (p.Gly37Val), rs1684393209, ClinGen CA347656095, ClinVar RCV003380268, REVEL 0.67, CADD 23.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- G37G (p.Gly37Gly), rs1573977865, gnomAD 2-96265271-G-A, AlphaMissense 0.13, MetaLR 0.19
- G37C (p.Gly37Cys), gnomAD 2-96265273-C-A, REVEL 0.76, CADD 28.90
- G37S (p.Gly37Ser), gnomAD 2-96265273-C-T, REVEL 0.61, CADD 23.80
- A38P (p.Ala38Pro), rs1456398772, ClinGen CA347656091, ClinVar RCV002014428, TOPMed rs1456398772, REVEL 0.65, CADD 25.30, Uncertain significance, Hereditary pheochromocytoma and paraganglioma
- A38S (p.Ala38Ser), rs1456398772, ClinGen CA347656090, ClinVar RCV001071122, ClinVar RCV002320353, REVEL 0.39, CADD 23.10, Uncertain significance, Pheochromocytoma; Hereditary pheochromocytoma and paraganglioma; Hereditary canc
- A38T (p.Ala38Thr), rs1456398772, ClinGen CA347656092, ClinVar RCV003165018, ClinVar RCV003778938, REVEL 0.35, CADD 22.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary pheochromocytoma and paragan
- A38A (p.Ala38Ala), gnomAD 2-96265268-G-T, AlphaMissense 0.09, MetaLR 0.07
- A38V (p.Ala38Val), gnomAD 2-96265269-G-A, REVEL 0.40, CADD 22.50
Public TMEM127 analysis runs
- TMEM127 analysis run — TMEM127 (1,049 variants) — completed 2026-08-21