MMADHC (Q9H3L0) variants and mutations
MMADHC (also known as Q9H3L0) is a human protein-coding gene encoding a cobalamin trafficking protein CblD protein. It directs intracellular cobalamin toward the methylcobalamin and adenosylcobalamin pathways needed for methionine and methylmalonyl-CoA metabolism. Biallelic pathogenic variants cause cblD disease, producing isolated or combined methylmalonic acidemia and homocystinuria. This analysis covers 595 MMADHC variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes methylmalonic aciduria and homocystinuria type cblD, Methylmalonic acidemia with homocystinuria, type cblD, and Methylmalonic acidemia with homocystinuria. Example MMADHC variants include A2T, A2V, and N3=.
Variant analysis overview
- Gene: MMADHC
- Protein: Q9H3L0
- UniProt accession: Q9H3L0
- Organism: Homo sapiens
- Variants analyzed: 595
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 386 unspecified-consequence records; 1 stop retained variant; 50 synonymous variants; 22 frameshift variants; 122 missense variants; 1 in-frame insertions; 4 in-frame deletions; 3 splice-region variants; 6 stop-gained variants; 2 substitution
- Prediction scores: 471 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: methylmalonic aciduria and homocystinuria type cblD, Methylmalonic acidemia with homocystinuria, type cblD, Methylmalonic acidemia with homocystinuria, homocystinuria without methylmalonic aciduria, methylmalonic aciduria and/or homocystinuria, cblD type, Methylmalonic acidemia with homocystinuria, type cblC, methylmalonic aciduria and homocystinuria type cblC, homocystinuria-megaloblastic anemia cblD type, isolated methylmalonic aciduria cblD type, inborn disorder of cobalamin metabolism and transport, methylcobalamin deficiency type cblDv1, vitamin B12-responsive methylmalonic acidemia, type cblDv2.
Protein structure and variant hotspots
- Protein features: 1 post-translational modification sites.
- PTM context: 4 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 MMADHC variants
Examples include A2T, A2V, N3=, N3D, N3H, N3K, N3S, V4M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), ExAC rs753911939, gnomAD rs753911939, REVEL 0.59, CADD 19.00
- A2V (p.Ala2Val), gnomAD rs1308795683, REVEL 0.57, CADD 22.80
- N3=, NCI-TCGA Cosmic COSV5757, Variant assessed as somatic; low impact.
- N3D (p.Asn3Asp), ExAC rs764550264, gnomAD rs764550264, REVEL 0.19, CADD 18.40
- N3H (p.Asn3His), ExAC rs764550264, gnomAD rs764550264, REVEL 0.18, CADD 17.70
- N3K (p.Asn3Lys), ExAC rs756642186, TOPMed rs756642186, gnomAD rs756642186, REVEL 0.19, CADD 17.10
- N3S (p.Asn3Ser), TOPMed rs529455427, gnomAD rs529455427, REVEL 0.14, CADD 7.52, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- V4M (p.Val4Met), ESP rs371740443, TOPMed rs371740443, gnomAD rs371740443, REVEL 0.49, CADD 26.40
- L5P (p.Leu5Pro), gnomAD rs1457237939, REVEL 0.95, CADD 27.90
- C6F (p.Cys6Phe), TOPMed rs1159486541, gnomAD rs1159486541, REVEL 0.77, CADD 22.80
- C6R (p.Cys6Arg), TOPMed rs1452262242
- C6S (p.Cys6Ser), TOPMed rs1159486541, gnomAD rs1159486541
- C6Y (p.Cys6Tyr), cosmic curated COSV57574
- N7S (p.Asn7Ser), TOPMed rs1389820565, gnomAD rs1389820565, REVEL 0.23, CADD 17.10
- N7T (p.Asn7Thr), TOPMed rs1389820565, gnomAD rs1389820565, REVEL 0.32, CADD 21.60
- N7Y (p.Asn7Tyr), TOPMed rs1395336239, REVEL 0.54, CADD 23.00
- R10T (p.Arg10Thr), cosmic curated COSV57573
- V12A (p.Val12Ala), gnomAD rs1682805804, REVEL 0.69, CADD 26.50
- V12I (p.Val12Ile), cosmic curated COSV57574, gnomAD rs1682805838, REVEL 0.36, CADD 20.40
- V12L (p.Val12Leu), NCI-TCGA Cosmic COSV5757, Variant assessed as somatic; moderate impact.
- S13F (p.Ser13Phe), ExAC rs777848447, TOPMed rs777848447, gnomAD rs777848447, REVEL 0.51, CADD 28.00
- S13Y (p.Ser13Tyr), ExAC rs777848447, TOPMed rs777848447, gnomAD rs777848447, REVEL 0.52, CADD 25.70
- Y14C (p.Tyr14Cys), rs756550492, ClinGen CA1902510, cosmic curated COSV57573, ClinVar RCV000805239, REVEL 0.80, CADD 27.60, Uncertain significance, not provided; Methylmalonic aciduria and homocystinuria type cblD
- Y14H (p.Tyr14His), TOPMed rs1682805675
- L15V (p.Leu15Val), 1000Genomes rs200819691, ExAC rs200819691, REVEL 0.26, CADD 19.30
- P16Q (p.Pro16Gln), cosmic curated COSV10030
- P16S (p.Pro16Ser), cosmic curated COSV57573, REVEL 0.62, CADD 22.60
- F18C (p.Phe18Cys), TOPMed rs1682805481, REVEL 0.81, CADD 24.80
- F18L (p.Phe18Leu), ExAC rs768073505, TOPMed rs768073505, gnomAD rs768073505, REVEL 0.29, CADD 20.40
- F18V (p.Phe18Val), ExAC rs768073505, TOPMed rs768073505, gnomAD rs768073505
- C19G (p.Cys19Gly), cosmic curated COSV10440, REVEL 0.15, CADD 19.70
- C19S (p.Cys19Ser), cosmic curated COSV10440
- C19W (p.Cys19Trp), TOPMed rs905523537, REVEL 0.24, CADD 21.30
- S20C (p.Ser20Cys), TOPMed rs1472806613, gnomAD rs1472806613
- S20F (p.Ser20Phe), TOPMed rs1472806613, gnomAD rs1472806613, REVEL 0.63, CADD 23.20
- L21S (p.Leu21Ser), TOPMed rs1238772425, gnomAD rs1238772425, REVEL 0.85, CADD 28.20
- L21V (p.Leu21Val), Ensembl rs1573880136
- V22I (p.Val22Ile), gnomAD rs1682804912, REVEL 0.22, CADD 19.00
- R24G (p.Arg24Gly), TOPMed rs904420258, gnomAD rs904420258, REVEL 0.85, CADD 27.60
- R24M (p.Arg24Met), cosmic curated COSV57574
- R24S (p.Arg24Ser), ExAC rs755350187, gnomAD rs755350187, REVEL 0.59, CADD 22.30
- R24T (p.Arg24Thr), gnomAD rs1206729629, REVEL 0.77, CADD 23.50
- V25F (p.Val25Phe), rs549522925, ClinGen CA312747, cosmic curated COSV57573, ClinVar RCV001035983, REVEL 0.75, CADD 24.80, Uncertain significance, Disorders of Intracellular Cobalamin Metabolism; Methylmalonic aciduria and homo
- V25L (p.Val25Leu), rs549522925, ClinGen CA58333608, ClinVar RCV001892458, ExAC rs549522925, REVEL 0.42, CADD 20.80, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- N27S (p.Asn27Ser), rs766017009, ClinGen CA1902506, ClinVar RCV001916592, ExAC rs766017009, REVEL 0.16, CADD 2.81, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- P28A (p.Pro28Ala), gnomAD rs1319731753, REVEL 0.24, CADD 16.30
- P28L (p.Pro28Leu), cosmic curated COSV10814
- K29E (p.Lys29Glu), ExAC rs762537066, gnomAD rs762537066, REVEL 0.36, CADD 23.80
- K29N (p.Lys29Asn), rs61750442, ClinGen CA1902504, ClinVar RCV000304535, ClinVar RCV000421018, REVEL 0.33, CADD 23.30, Benign/Likely benign, Disorders of Intracellular Cobalamin Metabolism; not specified; not provided
- A30D (p.Ala30Asp), ExAC rs764844761, gnomAD rs764844761
- A30T (p.Ala30Thr), gnomAD rs780143636, REVEL 0.16, CADD 17.40
- S32L (p.Ser32Leu), rs1434979492, NCI-TCGA Cosmic COSV5757, cosmic curated COSV57573, gnomAD rs1434979492, REVEL 0.82, CADD 28.20, Variant assessed as somatic; moderate impact.
- T33I (p.Thr33Ile), gnomAD rs1323175121, REVEL 0.48, CADD 24.10
- G35A (p.Gly35Ala), gnomAD rs1057389942, REVEL 0.65, CADD 23.90
- G35E (p.Gly35Glu), gnomAD rs1057389942, REVEL 0.64, CADD 23.20
- S36L (p.Ser36Leu), cosmic curated COSV57572, REVEL 0.65, CADD 24.10
- S37T (p.Ser37Thr), Ensembl rs11545265
- G38D (p.Gly38Asp), TOPMed rs1386535158, gnomAD rs1386535158, Uncertain significance
- G38R (p.Gly38Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G38V (p.Gly38Val), rs1386535158, ClinGen CA348871047, ClinVar RCV003063007, ClinVar RCV006363026, REVEL 0.77, CADD 24.10, Uncertain significance, Inborn genetic diseases; Methylmalonic aciduria and homocystinuria type cblD
- S39L (p.Ser39Leu), rs746785981, NCI-TCGA Cosmic COSV5757, cosmic curated COSV57574, ExAC rs746785981, REVEL 0.74, CADD 22.50, Variant assessed as somatic; moderate impact.
- D40G (p.Asp40Gly), gnomAD rs1248521016, REVEL 0.75, CADD 28.40
- E41* (p.Glu41Ter), cosmic curated COSV10732
- H43N (p.His43Asn), ExAC rs775175927, TOPMed rs775175927, gnomAD rs775175927, Uncertain significance
- H43P (p.His43Pro), ESP rs373627181, ExAC rs373627181, TOPMed rs373627181, gnomAD rs373627181, REVEL 0.61, CADD 21.70, Uncertain significance, Inborn genetic diseases
- H43Y (p.His43Tyr), rs775175927, ClinGen CA1902498, ClinVar RCV001885998, ClinVar RCV005660199, REVEL 0.23, CADD 16.90, Uncertain significance, Inborn genetic diseases; Methylmalonic aciduria and homocystinuria type cblD
- V44A (p.Val44Ala), gnomAD rs1245975393, REVEL 0.56, CADD 24.00
- V44L (p.Val44Leu), Ensembl rs1682803229
- A46G (p.Ala46Gly), Ensembl rs1573880040
- A46P (p.Ala46Pro), rs749521854, ClinGen CA1902496, ClinVar RCV000986829, ClinVar RCV005367652, REVEL 0.23, CADD 16.20, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD; Inborn genetic diseases
- P48H (p.Pro48His), cosmic curated COSV10030
- P48S (p.Pro48Ser), ExAC rs778041300, gnomAD rs778041300, REVEL 0.27, CADD 17.70
- P49L (p.Pro49Leu), ExAC rs769854836
- D50G (p.Asp50Gly), rs748278993, ClinGen CA1902493, ClinVar RCV003081841, ExAC rs748278993, REVEL 0.79, CADD 27.40, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- I51M (p.Ile51Met), Ensembl rs1682802665, REVEL 0.24, CADD 18.60
- I51T (p.Ile51Thr), rs755472574, ClinGen CA1902491, ClinVar RCV001341596, ExAC rs755472574, REVEL 0.43, CADD 21.00, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- I51V (p.Ile51Val), ExAC rs781704226, gnomAD rs781704226, REVEL 0.30, CADD 21.70
- R54* (p.Arg54Ter), rs118204047, ClinGen CA114489, NCI-TCGA Cosmic COSV5757, cosmic curated COSV57574, CADD 38.00, Pathogenic
- R54G (p.Arg54Gly), TOPMed rs118204047, gnomAD rs118204047, REVEL 0.75, CADD 24.00, Pathogenic
- R54L (p.Arg54Leu), cosmic curated COSV10732
- R54Q (p.Arg54Gln), rs1376956703, NCI-TCGA Cosmic COSV5757, cosmic curated COSV57573, TOPMed rs1376956703, REVEL 0.50, CADD 22.40, Variant assessed as somatic; moderate impact.
- T55A (p.Thr55Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V56A (p.Val56Ala), gnomAD rs1176730276, REVEL 0.56, CADD 23.20, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- V56G (p.Val56Gly), gnomAD rs1176730276, REVEL 0.69, CADD 23.50
- V56L (p.Val56Leu), Ensembl rs1682767724, Uncertain significance, Inborn genetic diseases
- V56M (p.Val56Met), rs1682767724, ClinGen CA348870933, ClinVar RCV001128925, ClinVar RCV001128926, REVEL 0.63, CADD 22.60, Uncertain significance, Disorders of Intracellular Cobalamin Metabolism; Methylmalonic aciduria and homo
- W57* (p.Trp57Ter), rs1682767587, ClinGen CA348870921, ClinVar RCV003600522, TOPMed rs1682767587, CADD 39.00, Pathogenic
- P58A (p.Pro58Ala), rs748188672, ClinGen CA1902471, ClinVar RCV003067903, ExAC rs748188672, REVEL 0.93, CADD 27.50, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- D59A (p.Asp59Ala), rs781154636, ClinGen CA348870910, ClinVar RCV002702807, REVEL 0.95, CADD 29.30, Uncertain significance, Inborn genetic diseases
- D59N (p.Asp59Asn), NCI-TCGA TCGA novel, REVEL 0.81, CADD 28.10, Variant assessed as somatic; moderate impact.
- D59V (p.Asp59Val), ExAC rs781154636, gnomAD rs781154636, REVEL 0.96, CADD 29.50
- E60* (p.Glu60Ter), TOPMed rs1181724331, gnomAD rs1181724331
- E60K (p.Glu60Lys), TOPMed rs1181724331, gnomAD rs1181724331, REVEL 0.60, CADD 23.40
- T61A (p.Thr61Ala), gnomAD rs1036471862, REVEL 0.17, CADD 17.10
- T61I (p.Thr61Ile), ExAC rs747475934, gnomAD rs747475934, REVEL 0.17, CADD 18.30
- T61S (p.Thr61Ser), ExAC rs747475934, gnomAD rs747475934, REVEL 0.14, CADD 14.40
- M62I (p.Met62Ile), TOPMed rs1682767231, cosmic curated COSV10030, REVEL 0.79, CADD 24.80, Uncertain significance, Inborn genetic diseases
- M62T (p.Met62Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M62V (p.Met62Val), rs780676909, ClinGen CA1902467, cosmic curated COSV57574, ClinVar RCV002972358, REVEL 0.86, CADD 25.30, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- G63* (p.Gly63Ter), cosmic curated COSV57574
- P64H (p.Pro64His), cosmic curated COSV57573
- P64S (p.Pro64Ser), ESP rs138571795, ExAC rs138571795, TOPMed rs138571795, gnomAD rs138571795, REVEL 0.88, CADD 24.80
- G66R (p.Gly66Arg), rs1334273037, TOPMed rs1334273037, ClinGen CA348870867, ClinVar RCV001982314, AlphaMissense 0.93, MetaLR 0.86, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- P67L (p.Pro67Leu), NCI-TCGA Cosmic COSV5757, cosmic curated COSV57573, Variant assessed as somatic; moderate impact.
- P67T (p.Pro67Thr), TOPMed rs1682767125, REVEL 0.91, CADD 26.90
- Q68* (p.Gln68Ter), rs2467645024, ClinGen CA348870854, ClinVar RCV002716105, Pathogenic
- Q68P (p.Gln68Pro), gnomAD rs1257043449, REVEL 0.84, CADD 23.40
- Q68R (p.Gln68Arg), cosmic curated COSV57574
- D69N (p.Asp69Asn), cosmic curated COSV57575
- Q70H (p.Gln70His), TOPMed rs1390472205, gnomAD rs1390472205, REVEL 0.36, CADD 20.20
- R71K (p.Arg71Lys), cosmic curated COSV10514, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- R71M (p.Arg71Met), cosmic curated COSV10732
- F72L (p.Phe72Leu), TOPMed rs1227369889, gnomAD rs1227369889, REVEL 0.88, CADD 24.90
- Q73H (p.Gln73His), gnomAD rs1350765416
- Q73R (p.Gln73Arg), TOPMed rs1008765976, gnomAD rs1008765976, REVEL 0.76, CADD 24.30
- P75L (p.Pro75Leu), ExAC rs756998611, gnomAD rs756998611, REVEL 0.94, CADD 29.60
- I78M (p.Ile78Met), Ensembl rs11545269
- I78V (p.Ile78Val), ExAC rs753336371, TOPMed rs753336371, gnomAD rs753336371, REVEL 0.21, CADD 16.70
- G79D (p.Gly79Asp), rs566530487, ClinGen CA58333333, ClinVar RCV002708259, TOPMed rs566530487, REVEL 0.92, CADD 26.30, Uncertain significance, Inborn genetic diseases
- D81E (p.Asp81Glu), TOPMed rs1302637256, gnomAD rs1302637256, REVEL 0.37, CADD 16.40
- D81H (p.Asp81His), NCI-TCGA Cosmic COSV5757, Variant assessed as somatic; moderate impact.
- D81N (p.Asp81Asn), cosmic curated COSV57574
- C82G (p.Cys82Gly), rs760590651, ClinGen CA1902460, ClinVar RCV000298719, ClinVar RCV000353552, REVEL 0.80, CADD 24.40, Uncertain significance, Disorders of Intracellular Cobalamin Metabolism; Methylmalonic aciduria and homo
- C82Y (p.Cys82Tyr), rs368471008, ClinGen CA1902459, ClinVar RCV002647731, ClinVar RCV005377319, REVEL 0.80, CADD 25.30, Uncertain significance, Inborn genetic diseases; Methylmalonic aciduria and homocystinuria type cblD
- N85S (p.Asn85Ser), rs767542742, ClinGen CA1902458, ClinVar RCV000338725, ClinVar RCV000392417, REVEL 0.21, CADD 17.70, Uncertain significance, Disorders of Intracellular Cobalamin Metabolism; Inborn genetic diseases; Methyl
- A88S (p.Ala88Ser), 1000Genomes rs550055732, ExAC rs550055732, gnomAD rs550055732, REVEL 0.29, CADD 0.14
- S89L (p.Ser89Leu), gnomAD rs1365707483, REVEL 0.21, CADD 18.50
- Q90* (p.Gln90Ter), rs1185711564, ClinVar RCV004576197, gnomAD rs1185711564, CADD 38.00, Likely pathogenic
- K91E (p.Lys91Glu), TOPMed rs1573878711
- K92E (p.Lys92Glu), TOPMed rs1221832070
- S93T (p.Ser93Thr), TOPMed rs1682764734
- L94M (p.Leu94Met), ExAC rs774165572, TOPMed rs774165572, gnomAD rs774165572, REVEL 0.30, CADD 22.70
- V95A (p.Val95Ala), gnomAD rs1185954801, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- V95L (p.Val95Leu), ExAC rs769956575, gnomAD rs769956575, REVEL 0.27, CADD 12.20
- H96Q (p.His96Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K97T (p.Lys97Thr), Ensembl rs915273753
- T98S (p.Thr98Ser), ExAC rs762037517, gnomAD rs762037517, REVEL 0.15, CADD 15.80
- L99F (p.Leu99Phe), Ensembl rs1558847878, REVEL 0.50, CADD 17.50
- P100L (p.Pro100Leu), rs776707322, ClinGen CA1902453, ClinVar RCV002923817, ExAC rs776707322, REVEL 0.91, CADD 29.50, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- D101Y (p.Asp101Tyr), ExAC rs768614592
- V102I (p.Val102Ile), gnomAD rs1209705053, REVEL 0.21, CADD 15.40
- L103V (p.Leu103Val), TOPMed rs1682764229
- A104E (p.Ala104Glu), 1000Genomes rs533388008, ExAC rs533388008, TOPMed rs533388008, gnomAD rs533388008, Uncertain significance
- A104G (p.Ala104Gly), 1000Genomes rs533388008, ExAC rs533388008, TOPMed rs533388008, gnomAD rs533388008, REVEL 0.25, CADD 18.20, Uncertain significance
- A104P (p.Ala104Pro), gnomAD rs1353312671
- A104V (p.Ala104Val), rs533388008, ClinGen CA1902451, ClinVar RCV001062191, ClinVar RCV003160503, REVEL 0.28, CADD 18.90, Uncertain significance, Inborn genetic diseases; Methylmalonic aciduria and homocystinuria type cblD
- P106L (p.Pro106Leu), ExAC rs775838388, gnomAD rs775838388, REVEL 0.82, CADD 24.80
- L107V (p.Leu107Val), gnomAD rs1320703293, REVEL 0.16, CADD 15.80
- S108L (p.Ser108Leu), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, Variant assessed as somatic; moderate impact., in MACD
- S109R (p.Ser109Arg), gnomAD rs1339360102, REVEL 0.23, CADD 20.30
- E110Q (p.Glu110Gln), cosmic curated COSV10514
- H112Q (p.His112Gln), ExAC rs746192843, TOPMed rs746192843, gnomAD rs746192843, REVEL 0.52, CADD 12.00, Uncertain significance, Inborn genetic diseases
- H112R (p.His112Arg), rs774720255, ExAC rs774720255, gnomAD rs774720255, REVEL 0.78, CADD 24.70, Variant assessed as somatic; moderate impact.
- E113Q (p.Glu113Gln), gnomAD rs1682763414, REVEL 0.29, CADD 20.90
- F114L (p.Phe114Leu), gnomAD rs1362894279, Likely benign
- M116I (p.Met116Ile), Ensembl rs2105048134
- A117V (p.Ala117Val), ExAC rs779439863, TOPMed rs779439863, gnomAD rs779439863, REVEL 0.82, CADD 29.50, Uncertain significance, Inborn genetic diseases
- Q118* (p.Gln118Ter), rs2105048127, ClinGen CA348870522, ClinVar RCV001951055, Ensembl rs2105048127, CADD 40.00, Pathogenic
- Y119H (p.Tyr119His), Ensembl rs1682763167
- V120M (p.Val120Met), rs756908515, NCI-TCGA Cosmic COSV1003, cosmic curated COSV10030, ExAC rs756908515, REVEL 0.42, CADD 23.90, Variant assessed as somatic; moderate impact.
- N121D (p.Asn121Asp), cosmic curated COSV57573
- N121K (p.Asn121Lys), gnomAD rs1161677408, REVEL 0.36, CADD 21.40
- N121S (p.Asn121Ser), rs2467644786, ClinGen CA348870497, ClinVar RCV002825200, REVEL 0.25, CADD 23.10, Uncertain significance, Methylmalonic aciduria and homocystinuria type cblD
- E122K (p.Glu122Lys), rs777544556, ClinGen CA1902444, ClinVar RCV001091564, ClinVar RCV002555952, REVEL 0.84, CADD 27.90, Uncertain significance, not provided; Methylmalonic aciduria and homocystinuria type cblD
- Q124L (p.Gln124Leu), rs886042982, ClinGen CA10604954, ClinVar RCV000323620, TOPMed rs886042982, REVEL 0.57, CADD 26.70, Uncertain significance, not provided
- G125D (p.Gly125Asp), ExAC rs775651062
- G125R (p.Gly125Arg), rs760971849, ClinGen CA1902417, ClinVar RCV001135920, ClinVar RCV001135921, REVEL 0.56, CADD 22.60, Uncertain significance, Disorders of Intracellular Cobalamin Metabolism; Methylmalonic aciduria and homo
- G125S (p.Gly125Ser), ExAC rs760971849, TOPMed rs760971849, gnomAD rs760971849, REVEL 0.35, CADD 16.90, Uncertain significance
- N126D (p.Asn126Asp), ExAC rs767705559, gnomAD rs767705559, REVEL 0.11, CADD 16.90
- D127V (p.Asp127Val), TOPMed rs1682721448
- A128S (p.Ala128Ser), gnomAD rs1215070978
- A128V (p.Ala128Val), gnomAD rs1341440892, REVEL 0.22, CADD 12.50
- P129L (p.Pro129Leu), Ensembl rs2105046158
- P129S (p.Pro129Ser), ESP rs367779384, ExAC rs367779384, gnomAD rs367779384, REVEL 0.32, CADD 21.30
- V130F (p.Val130Phe), NCI-TCGA TCGA novel, TOPMed rs1682721277, gnomAD rs1682721277, REVEL 0.27, CADD 17.00, Uncertain significance, Isolated methylmalonic aciduria cblD type
- E131D (p.Glu131Asp), TOPMed rs1682721203, REVEL 0.08, CADD 17.90, Likely benign
- E131G (p.Glu131Gly), TOPMed rs1294350745, REVEL 0.27, CADD 23.30
- Q132P (p.Gln132Pro), TOPMed rs1232191985, gnomAD rs1232191985, REVEL 0.61, CADD 22.80
- Q132R (p.Gln132Arg), TOPMed rs1232191985, gnomAD rs1232191985, REVEL 0.47, CADD 22.50
- E133G (p.Glu133Gly), Ensembl rs1682720947
Public MMADHC analysis runs
- MMADHC analysis run — MMADHC (595 variants) — completed 2026-08-21