RET (P07949) variants and mutations
RET (also known as P07949) is a human protein-coding gene encoding a proto-oncogene tyrosine-protein kinase receptor protein. Its activation by GDNF-family ligands guides development of the enteric nervous system, kidney, and other tissues. Activating variants cause multiple endocrine neoplasia type 2 and can drive cancer, whereas loss-of-function variants are an important cause of Hirschsprung disease. This analysis covers 4,409 RET variants and mutations. Of these, 51% have computational variant effect predictions. Disease context includes medullary thyroid gland carcinoma, multiple endocrine neoplasia type 2A, and multiple endocrine neoplasia type 2B. Example RET variants include M1?, A2E, and A2G.
Variant analysis overview
- Gene: RET
- Protein: P07949
- UniProt accession: P07949
- Organism: Homo sapiens
- Variants analyzed: 4409
- Variant scope: all variants
- Completed: 2026-08-09
Variant and mutation evidence
- Variant composition: 4,274 unspecified-consequence records; 48 missense variants; 6 frameshift variants; 68 synonymous variants; 5 in-frame insertions; 3 in-frame deletions; 3 splice-region variants; 1 stop-gained variants; 1 substitution
- Prediction scores: 2,246 variants have prediction scores (51% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: medullary thyroid gland carcinoma, multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, Hirschsprung disease, pheochromocytoma, multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma, non-small cell lung carcinoma, hepatocellular carcinoma, multiple endocrine neoplasia, colorectal cancer, gastrointestinal stromal tumor.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 24 binding sites; 26 post-translational modification sites.
- Structural context: 1,574 variants have structural context.
- PTM context: 107 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 RET variants
Examples include M1?, A2E, A2G, A2V, A2T, A2S, A2A, K3E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A2E (p.Ala2Glu), rs1837063635, ClinGen CA376768001, ClinVar RCV003647159, ClinVar RCV004661757, REVEL 0.29, MetaLR 0.89, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- A2G (p.Ala2Gly), Ensembl rs1837063635, MetaLR 0.89, MetaSVM 0.71, Uncertain significance
- A2V (p.Ala2Val), Ensembl rs1837063635, REVEL 0.30, MetaLR 0.86, Uncertain significance, Hereditary cancer-predisposing syndrome
- A2T (p.Ala2Thr), gnomAD 10-43077262-G-A, REVEL 0.34, MetaLR 0.89
- A2S (p.Ala2Ser), gnomAD 10-43077262-G-T, REVEL 0.31, MetaLR 0.89
- A2A (p.Ala2Ala), gnomAD 10-43077264-G-T, CADD 15.60
- K3E (p.Lys3Glu), rs1564480827, ClinGen CA376768005, ClinVar RCV000708761, ClinVar RCV001213441, REVEL 0.16, MetaLR 0.87, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- K3R (p.Lys3Arg), gnomAD 10-43077264-GA-G, CADD 26.90
- K3T (p.Lys3Thr), gnomAD 10-43077266-A-C, REVEL 0.18, MetaLR 0.84
- K3M (p.Lys3Met), gnomAD 10-43077266-A-T, REVEL 0.24, MetaLR 0.87
- K3N (p.Lys3Asn), gnomAD 10-43077267-G-T, REVEL 0.16, MetaLR 0.86
- A4E (p.Ala4Glu), cosmic curated COSV60686, Ensembl rs1837063876, REVEL 0.38, MetaLR 0.91, Uncertain significance
- A4T (p.Ala4Thr), rs1837063785, ClinGen CA376768012, ClinVar RCV001323974, ClinVar RCV003382525, REVEL 0.26, MetaLR 0.88, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- A4V (p.Ala4Val), rs1837063876, ClinGen CA376768017, cosmic curated COSV60702, ClinVar RCV001066496, REVEL 0.33, MetaLR 0.88, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- A4S (p.Ala4Ser), gnomAD 10-43077268-G-T, REVEL 0.24, MetaLR 0.84
- A4A (p.Ala4Ala), rs2132497433, gnomAD 10-43077270-G-A, CADD 16.20
- T5A (p.Thr5Ala), rs2132497461, ClinGen CA376768019, ClinVar RCV002389230, ClinVar RCV003095091, REVEL 0.18, MetaLR 0.84, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- T5K (p.Thr5Lys), gnomAD rs1444096302, REVEL 0.18, AlphaMissense 0.22, Uncertain significance
- T5M (p.Thr5Met), rs1444096302, ClinGen CA376768023, ClinVar RCV002003551, ClinVar RCV002388990, REVEL 0.23, AlphaMissense 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- T5P (p.Thr5Pro), 1000Genomes rs2132497461, Uncertain significance
- T5R (p.Thr5Arg), rs1444096302, ClinGen CA376768022, ClinVar RCV001042075, gnomAD rs1444096302, AlphaMissense 0.22, MetaLR 0.84, Uncertain significance, Multiple endocrine neoplasia, type 2
- T5S (p.Thr5Ser), gnomAD 10-43077271-A-T, REVEL 0.17, MetaLR 0.81
- T5T (p.Thr5Thr), rs1226499208, gnomAD 10-43077273-G-A, CADD 14.00
- S6A (p.Ser6Ala), rs1588848475, ClinGen CA376768026, ClinVar RCV000811238, ClinVar RCV005712272, AlphaMissense 0.05, MetaLR 0.83, Conflicting interpretations, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- S6P (p.Ser6Pro), rs1588848475, ClinGen CA376768025, ClinVar RCV001309613, ClinVar RCV004951495, REVEL 0.17, AlphaMissense 0.05, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- S6T (p.Ser6Thr), cosmic curated COSV60686, Ensembl rs1588848475, Uncertain significance
- S6Y (p.Ser6Tyr), gnomAD 10-43077275-C-A, REVEL 0.34, MetaLR 0.89
- S6F (p.Ser6Phe), gnomAD 10-43077275-C-T, REVEL 0.37, MetaLR 0.90
- S6S (p.Ser6Ser), rs1185431356, gnomAD 10-43077276-C-A, CADD 15.40
- G7D (p.Gly7Asp), rs1366681125, ClinGen CA376768033, ClinVar RCV000567089, ClinVar RCV000688487, REVEL 0.33, MetaLR 0.91, Conflicting interpretations, Pheochromocytoma; Hirschsprung disease, susceptibility to, 1; Multiple endocrine
- G7R (p.Gly7Arg), rs1257661718, ClinGen CA376768031, ClinVar RCV003534166, REVEL 0.26, MetaLR 0.89, Uncertain significance, Multiple endocrine neoplasia, type 2
- G7S (p.Gly7Ser), rs1257661718, ClinGen CA376768030, ClinVar RCV001297483, ClinVar RCV003373102, REVEL 0.23, MetaLR 0.89, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- G7V (p.Gly7Val), rs1366681125, ClinGen CA376768035, ClinVar RCV001916021, TOPMed rs1366681125, REVEL 0.43, MetaLR 0.91, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- G7A (p.Gly7Ala), gnomAD 10-43077276-CGGTG, CADD 30.00
- G7C (p.Gly7Cys), gnomAD 10-43077277-G-T, REVEL 0.48, MetaLR 0.93
- G7G (p.Gly7Gly), gnomAD 10-43077279-T-C, CADD 15.10
- A8S (p.Ala8Ser), rs1476325851, ClinGen CA376768038, ClinVar RCV001044660, ClinVar RCV002429602, REVEL 0.18, MetaLR 0.86, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- A8T (p.Ala8Thr), gnomAD rs1476325851, REVEL 0.19, MetaLR 0.86, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- A8V (p.Ala8Val), rs1168334949, ClinGen CA376768041, cosmic curated COSV10039, ClinVar RCV002450247, REVEL 0.23, MetaLR 0.89, Uncertain significance, Hereditary cancer-predisposing syndrome
- A8D (p.Ala8Asp), gnomAD 10-43077281-C-A, REVEL 0.26, MetaLR 0.87
- A8A (p.Ala8Ala), gnomAD 10-43077282-C-A, CADD 15.20
- A9G (p.Ala9Gly), cosmic curated COSV10968, Ensembl rs2132497909, REVEL 0.19, MetaLR 0.87
- A9S (p.Ala9Ser), rs2132497871, ClinGen CA376768043, ClinVar RCV004011854, REVEL 0.16, MetaLR 0.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- A9T (p.Ala9Thr), Ensembl rs2132497871, REVEL 0.17, MetaLR 0.90
- A9P (p.Ala9Pro), gnomAD 10-43077283-G-C, REVEL 0.33, MetaLR 0.93
- A9E (p.Ala9Glu), gnomAD 10-43077284-C-A, REVEL 0.28, MetaLR 0.91
- A9V (p.Ala9Val), gnomAD 10-43077284-C-T, REVEL 0.17, MetaLR 0.84
- A9A (p.Ala9Ala), gnomAD 10-43077285-G-T, CADD 13.60
- G10A (p.Gly10Ala), rs1303812507, ClinGen CA376768051, ClinVar RCV001949764, ClinVar RCV004946896, REVEL 0.36, MetaLR 0.96, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- G10E (p.Gly10Glu), rs1303812507, ClinGen CA376768053, ClinVar RCV001338708, ClinVar RCV002438769, REVEL 0.46, MetaLR 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- G10R (p.Gly10Arg), rs2132497960, ClinGen CA376768048, ClinVar RCV003534112, Ensembl rs2132497960, REVEL 0.47, MetaLR 0.96, Uncertain significance, Multiple endocrine neoplasia, type 2
- G10V (p.Gly10Val), rs1303812507, ClinGen CA376768052, ClinVar RCV001205118, ClinVar RCV005268942, REVEL 0.57, MetaLR 0.95, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- G10W (p.Gly10Trp), NCI-TCGA TCGA novel, REVEL 0.52, MetaLR 0.96, Variant assessed as somatic; moderate impact.
- p.Gly10 Leu11insValGlyAlaGlnAsn, gnomAD 10-43077288-G-GGT, CADD 19.20
- G10G (p.Gly10Gly), gnomAD 10-43077288-G-C, CADD 14.50
- L11M (p.Leu11Met), rs587780812, ClinGen CA206710333, ClinVar RCV000575741, ClinVar RCV000689589, REVEL 0.22, MetaLR 0.94, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; Pheochromocytoma
- L11R (p.Leu11Arg), Ensembl rs2132498173, REVEL 0.53, MetaLR 0.94
- L11V (p.Leu11Val), rs587780812, ClinGen CA009216, ClinVar RCV000123319, ClinVar RCV001019149, REVEL 0.14, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- L11C (p.Leu11Cys), gnomAD 10-43077284-CG-C, CADD 23.40
- L11L (p.Leu11Leu), rs587780812, gnomAD 10-43077289-C-T, CADD 14.20
- L11P (p.Leu11Pro), gnomAD 10-43077290-T-C, REVEL 0.60, MetaLR 0.95
- R12C (p.Arg12Cys), rs2132498232, ClinGen CA376768058, ClinVar RCV003646040, Ensembl rs2132498232, REVEL 0.38, MetaLR 0.79, Uncertain significance, Multiple endocrine neoplasia, type 2
- R12G (p.Arg12Gly), rs2132498232, ClinGen CA376768059, ClinVar RCV002049372, ClinVar RCV004656678, REVEL 0.40, MetaLR 0.73, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- R12H (p.Arg12His), rs2132498277, ClinGen CA376768060, ClinVar RCV002014081, Ensembl rs2132498277, REVEL 0.23, MetaLR 0.79, Uncertain significance, Multiple endocrine neoplasia, type 2
- R12S (p.Arg12Ser), gnomAD 10-43077292-C-A, REVEL 0.25, MetaLR 0.78
- R12L (p.Arg12Leu), gnomAD 10-43077293-G-T, REVEL 0.20, MetaLR 0.75
- R12P (p.Arg12Pro), gnomAD 10-43077293-G-C, REVEL 0.52, MetaLR 0.79
- L13M (p.Leu13Met), gnomAD 10-43077295-C-A, REVEL 0.39, MetaLR 0.91
- L13L (p.Leu13Leu), gnomAD 10-43077295-C-T, CADD 8.08
- L13V (p.Leu13Val), gnomAD 10-43077295-C-G, REVEL 0.29, MetaLR 0.92
- L13P (p.Leu13Pro), gnomAD 10-43077296-T-C, REVEL 0.47, MetaLR 0.93
- L13Q (p.Leu13Gln), gnomAD 10-43077296-T-A, REVEL 0.33, MetaLR 0.93
- L14M (p.Leu14Met), Ensembl rs1564480876, REVEL 0.33, MetaLR 0.82
- L14P (p.Leu14Pro), rs2132498406, ClinGen CA376768071, ClinVar RCV001975787, ClinVar RCV004042196, REVEL 0.42, MetaLR 0.78, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- L14L (p.Leu14Leu), rs1564480876, gnomAD 10-43077298-C-T, CADD 7.51
- L14Q (p.Leu14Gln), gnomAD 10-43077299-T-A, REVEL 0.36, MetaLR 0.83
- p.Leu14 Leu15insTrp, rs2132498515, gnomAD 10-43077301-T-TGG, CADD 16.80
- L15F (p.Leu15Phe), TOPMed rs876660157, gnomAD rs876660157, REVEL 0.24, MetaLR 0.95, Likely benign
- L15S (p.Leu15Ser), rs2132498541, ClinGen CA376768076, ClinVar RCV001933804, Ensembl rs2132498541, REVEL 0.31, MetaLR 0.94, Uncertain significance, Multiple endocrine neoplasia, type 2
- L15L (p.Leu15Leu), rs1418746925, gnomAD 10-43077301-T-C, CADD 9.22
- L16A (p.Leu16Ala), rs2491935478, ClinGen CA2580081462, ClinVar RCV002342361, Pathogenic
- L16Q (p.Leu16Gln), rs1564480893, ClinGen CA376768082, ClinVar RCV000694092, ClinVar RCV003163176, REVEL 0.43, MetaLR 0.91, Uncertain significance, Hirschsprung disease, susceptibility to, 1; not provided; Hereditary cancer-pred
- L16V (p.Leu16Val), rs1309896929, ClinGen CA376768081, ClinVar RCV004524677, ClinVar RCV006488806, AlphaMissense 0.08, MetaLR 0.83, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- L16M (p.Leu16Met), gnomAD 10-43077304-C-A, REVEL 0.31, MetaLR 0.89
- L16L (p.Leu16Leu), rs1309896929, gnomAD 10-43077304-C-T, AlphaMissense 0.08, MetaLR 0.83
- L16P (p.Leu16Pro), gnomAD 10-43077305-T-C, REVEL 0.61, MetaLR 0.91
- L17M (p.Leu17Met), rs1328756940, ClinGen CA376768085, ClinVar RCV002343011, TOPMed rs1328756940, REVEL 0.34, MetaLR 0.95, Uncertain significance, Hereditary cancer-predisposing syndrome
- L17P (p.Leu17Pro), rs1837066964, ClinGen CA376768088, ClinVar RCV001343082, ClinVar RCV002245970, REVEL 0.63, MetaLR 0.96, Uncertain significance, Multiple endocrine neoplasia, type 2; Breast carcinoma; Family history of cancer
- L17C (p.Leu17Cys), gnomAD 10-43077306-GC-G, CADD 24.40
- L17L (p.Leu17Leu), rs1328756940, gnomAD 10-43077307-C-T, CADD 13.50
- L17Q (p.Leu17Gln), gnomAD 10-43077308-T-A, REVEL 0.43, MetaLR 0.96
- L18P (p.Leu18Pro), rs2132498957, ClinGen CA376768093, ClinVar RCV001988207, ClinVar RCV002344161, REVEL 0.48, MetaLR 0.93, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- p.Leu18 Leu19del, rs768132465, gnomAD 10-43077301-TTGCT, CADD 18.70
- L18A (p.Leu18Ala), gnomAD 10-43077308-TGC-T, CADD 26.90
- L18L (p.Leu18Leu), rs2132498926, gnomAD 10-43077310-C-T, CADD 14.70
- L18V (p.Leu18Val), gnomAD 10-43077310-C-G, REVEL 0.27, MetaLR 0.93
- L18M (p.Leu18Met), gnomAD 10-43077310-C-A, REVEL 0.35, MetaLR 0.95
- L18R (p.Leu18Arg), gnomAD 10-43077311-T-G, REVEL 0.50, MetaLR 0.94
- L19M (p.Leu19Met), rs2132499024, ClinGen CA376768095, ClinVar RCV002344878, REVEL 0.31, MetaLR 0.95, Uncertain significance, Hereditary cancer-predisposing syndrome
- L19P (p.Leu19Pro), rs2132499055, ClinGen CA376768098, ClinVar RCV003033756, ClinVar RCV003170897, REVEL 0.55, MetaLR 0.93, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- L19del (p.Leu19del), gnomAD 10-43077298-CTGT-, CADD 12.10
- p.Leu19dup, rs1564480881, gnomAD 10-43077298-C-CTG, CADD 11.90
- L19L (p.Leu19Leu), rs2132499024, gnomAD 10-43077313-C-T, CADD 14.90
- P20L (p.Pro20Leu), rs1837067697, ClinGen CA376768105, ClinVar RCV002012141, UniProt VAR 009459, REVEL 0.56, MetaLR 0.82, Uncertain significance, Multiple endocrine neoplasia, type 2
- P20Q (p.Pro20Gln), rs1837067697, ClinGen CA376768103, ClinVar RCV001224702, ClinVar RCV002356955, REVEL 0.25, MetaLR 0.85, Uncertain significance, Multiple endocrine neoplasia, type 2; Pheochromocytoma; Familial medullary thyro
- P20R (p.Pro20Arg), rs1837067697, ClinGen CA376768104, ClinVar RCV001240317, ClinVar RCV002357026, REVEL 0.39, MetaLR 0.86, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- P20S (p.Pro20Ser), rs1205904653, ClinGen CA376768100, cosmic curated COSV60702, ClinVar RCV000654562, REVEL 0.11, MetaLR 0.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- P20T (p.Pro20Thr), gnomAD rs1205904653, REVEL 0.29, MetaLR 0.82, Uncertain significance, in HSCR1
- p.Pro20 Leu21del, gnomAD 10-43077311-TGCTG, CADD 22.30
- p.Pro20dup, rs1064796534, gnomAD 10-43077314-T-TGC, CADD 22.40
- P20P (p.Pro20Pro), rs1263991822, gnomAD 10-43077318-G-C, CADD 14.90
- L21R (p.Leu21Arg), gnomAD rs1461009997, REVEL 0.52, MetaLR 0.95, Uncertain significance, Multiple endocrine neoplasia, type 2
- L21V (p.Leu21Val), Ensembl rs2132499288, MetaLR 0.94, MetaSVM 1.03, Likely benign
- L21P (p.Leu21Pro), gnomAD 10-43077320-T-C, REVEL 0.56, MetaLR 0.95
- L21L (p.Leu21Leu), rs944333660, gnomAD 10-43077321-G-A, CADD 13.80
- L22V (p.Leu22Val), Ensembl rs2132499388, MetaLR 0.87, MetaSVM 0.60
- L22L (p.Leu22Leu), gnomAD 10-43077322-C-T, CADD 14.50
- L22I (p.Leu22Ile), gnomAD 10-43077322-C-A, REVEL 0.17, MetaLR 0.86
- L22P (p.Leu22Pro), gnomAD 10-43077323-T-C, REVEL 0.56, MetaLR 0.91
- L22Q (p.Leu22Gln), gnomAD 10-43077323-T-A, REVEL 0.47, MetaLR 0.91
- G23D (p.Gly23Asp), rs1554815546, ClinGen CA376768119, ClinVar RCV000563458, ClinVar RCV001047359, REVEL 0.46, MetaLR 0.93, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- G23R (p.Gly23Arg), rs1198827347, ClinGen CA376768117, ClinVar RCV002369484, gnomAD rs1198827347, REVEL 0.41, MetaLR 0.95, Uncertain significance, Hereditary cancer-predisposing syndrome
- G23S (p.Gly23Ser), rs1198827347, ClinGen CA376768116, ClinVar RCV004017068, REVEL 0.16, MetaLR 0.87, Uncertain significance, Multiple endocrine neoplasia, type 2
- G23V (p.Gly23Val), rs1554815546, ClinGen CA376768121, ClinVar RCV001222560, ClinVar RCV002375209, REVEL 0.46, MetaLR 0.95, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- G23C (p.Gly23Cys), gnomAD 10-43077325-G-T, REVEL 0.42, MetaLR 0.95
- G23A (p.Gly23Ala), gnomAD 10-43077326-G-C, REVEL 0.31, MetaLR 0.88
- G23G (p.Gly23Gly), gnomAD 10-43077327-C-A, CADD 14.60
- K24E (p.Lys24Glu), rs1263923038, ClinGen CA376768124, ClinVar RCV002367339, gnomAD rs1263923038, REVEL 0.17, MetaLR 0.70, Likely benign, Hereditary cancer-predisposing syndrome
- K24R (p.Lys24Arg), gnomAD 10-43077329-A-G, REVEL 0.16, MetaLR 0.82
- K24K (p.Lys24Lys), rs1448705985, gnomAD 10-43077330-A-G, CADD 22.70
- K24N (p.Lys24Asn), gnomAD 10-43077330-A-T, REVEL 0.14, MetaLR 0.82
- V25W (p.Val25Trp), gnomAD 10-43077327-CA-C, CADD 23.80
- V25L (p.Val25Leu), gnomAD 10-43077331-G-C, REVEL 0.19, MetaLR 0.25
- V25M (p.Val25Met), gnomAD 10-43077331-G-A, REVEL 0.23, MetaLR 0.36
- V25V (p.Val25Val), rs2132656259, gnomAD 10-43100460-G-A, CADD 9.23
- A26E (p.Ala26Glu), Ensembl rs2132656365, Uncertain significance
- A26G (p.Ala26Gly), Ensembl rs2132656365, Uncertain significance
- A26P (p.Ala26Pro), Ensembl rs1554817350, Uncertain significance
- A26S (p.Ala26Ser), rs1554817350, ClinGen CA376770037, ClinVar RCV000546416, ClinVar RCV004944011, REVEL 0.12, AlphaMissense 0.05, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- A26T (p.Ala26Thr), rs1554817350, ClinGen CA376770035, ClinVar RCV002740314, ClinVar RCV004656972, AlphaMissense 0.05, MetaLR 0.23, Uncertain significance, Multiple endocrine neoplasia, type 2; Hereditary cancer-predisposing syndrome
- A26V (p.Ala26Val), rs2132656365, ClinGen CA376770040, cosmic curated COSV10887, ClinVar RCV003876184, REVEL 0.14, MetaLR 0.37, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2; n
- L27F (p.Leu27Phe), ESP rs369519655, ExAC rs369519655, TOPMed rs369519655, gnomAD rs369519655, Likely benign
- L27M (p.Leu27Met), ESP rs377160777, ExAC rs377160777, TOPMed rs377160777, gnomAD rs377160777, Likely benign
- L27V (p.Leu27Val), ESP rs377160777, ExAC rs377160777, TOPMed rs377160777, gnomAD rs377160777, Likely benign
- L27W (p.Leu27Trp), Ensembl rs2132656469
- L27L (p.Leu27Leu), rs377160777, gnomAD 10-43100464-T-C, CADD 2.93
- L27S (p.Leu27Ser), gnomAD 10-43100465-T-C, REVEL 0.41, MetaLR 0.34
- G28A (p.Gly28Ala), Ensembl rs2132656587
- G28C (p.Gly28Cys), ExAC rs779905135, TOPMed rs779905135, gnomAD rs779905135, Benign
- G28D (p.Gly28Asp), Ensembl rs2132656587
- G28R (p.Gly28Arg), ExAC rs779905135, TOPMed rs779905135, gnomAD rs779905135, Benign
- G28S (p.Gly28Ser), rs779905135, ClinGen CA045033, ClinVar RCV000807337, ClinVar RCV002424881, REVEL 0.60, MetaLR 0.67, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2; P
- G28V (p.Gly28Val), Ensembl rs2132656587, MetaLR 0.66, MetaSVM 0.45
- L29F (p.Leu29Phe), NCI-TCGA TCGA novel, Ensembl rs2132656652, Variant assessed as somatic; moderate impact.
- L29H (p.Leu29His), Ensembl rs2132656690
- L29I (p.Leu29Ile), NCI-TCGA TCGA novel, Ensembl rs2132656652, Uncertain significance, Multiple endocrine neoplasia, type 2
- L29P (p.Leu29Pro), Ensembl rs2132656690
- L29V (p.Leu29Val), Ensembl rs2132656652, MetaLR 0.74, MetaSVM 0.50
- Y30* (p.Tyr30Ter), Ensembl rs1588862357, Likely benign
- Y30C (p.Tyr30Cys), rs2132656815, ClinGen CA376770063, ClinVar RCV001914533, ClinVar RCV004041123, AlphaMissense 0.24, MetaLR 0.73, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia, type 2
- Y30F (p.Tyr30Phe), Ensembl rs2132656815, Uncertain significance
- Y30H (p.Tyr30His), TOPMed rs1399243256, Uncertain significance, Hereditary cancer-predisposing syndrome
- Y30N (p.Tyr30Asn), TOPMed rs1399243256
- Y30S (p.Tyr30Ser), Ensembl rs2132656815, MetaLR 0.75, MetaSVM 0.55, Uncertain significance
- Y30Y (p.Tyr30Tyr), rs1588862357, gnomAD 10-43100475-C-T, CADD 9.33
- F31I (p.Phe31Ile), Ensembl rs2132656898, Uncertain significance, Multiple endocrine neoplasia, type 2
- F31L (p.Phe31Leu), Ensembl rs2132656948, Uncertain significance, Hereditary cancer-predisposing syndrome
- F31S (p.Phe31Ser), Ensembl rs2132656926, MetaLR 0.65, MetaSVM 0.33
- S32* (p.Ser32Ter), Ensembl rs76764689, Likely pathogenic, in HSCR1
- S32L (p.Ser32Leu), rs76764689, ClinGen CA009398, ClinVar RCV000014948, ClinVar RCV000678742, REVEL 0.43, MetaLR 0.31, Likely pathogenic, Multiple endocrine neoplasia, type 2; Hirschsprung disease, susceptibility to, 1
- S32P (p.Ser32Pro), Ensembl rs2132657005
- S32T (p.Ser32Thr), Ensembl rs2132657005
- S32W (p.Ser32Trp), Ensembl rs76764689, Uncertain significance, RET-related disorder
- S32S (p.Ser32Ser), rs139821724, gnomAD 10-43100481-G-A, CADD 1.53
- R33G (p.Arg33Gly), Ensembl rs2132657133
- R33K (p.Arg33Lys), Ensembl rs2132657164, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R33M (p.Arg33Met), Ensembl rs2132657164
- R33S (p.Arg33Ser), ExAC rs768485233, gnomAD rs768485233
- R33T (p.Arg33Thr), Ensembl rs2132657164
Public RET analysis runs
- RET analysis run — RET (4,409 variants) — completed 2026-08-09