UNC13D (Protein unc-13 homolog D) variants and mutations
UNC13D (also known as Protein unc-13 homolog D) is a human protein-coding gene encoding a protein unc-13 homolog D protein. It primes cytotoxic granules for membrane fusion in natural-killer cells and cytotoxic T cells, enabling release of perforin and granzymes. Biallelic loss-of-function variants cause familial hemophagocytic lymphohistiocytosis type 3 with uncontrolled immune activation. This analysis covers 1,629 UNC13D variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Familial hemophagocytic lymphohistiocytosis, autoinflammatory syndrome, and hereditary hemophagocytic lymphohistiocytosis. Example UNC13D variants include A2V, L5F, and L5P.
Variant analysis overview
- Gene: UNC13D
- Protein: Protein unc-13 homolog D
- UniProt accession: Q70J99
- Organism: Homo sapiens
- Variants analyzed: 1629
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,437 unspecified-consequence records; 2 stop lost; 46 synonymous variants; 125 missense variants; 9 frameshift variants; 7 stop-gained variants; 4 in-frame deletions; 2 splice-region variants; 1 substitution
- Prediction scores: 1,261 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Familial hemophagocytic lymphohistiocytosis, autoinflammatory syndrome, hereditary hemophagocytic lymphohistiocytosis, neurodegenerative disease, cardiovascular disorder, coronary artery disorder, hereditary disease, response to statin, Hypercholesterolemia, metabolic disease, asthma, adult onset asthma.
Protein structure and variant hotspots
- Protein features: 4 domains; 13 binding sites; 1 post-translational modification sites.
- Structural context: 689 variants have structural context.
- PTM context: 3 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, MaveDB, LitVar.
Notable UNC13D variants
Examples include A2V, L5F, L5P, S6F, H7Y, P8L, Q10H, R11C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2V (p.Ala2Val), rs752295384, ClinGen CA8773703, cosmic curated COSV52887, ClinVar RCV001967088, REVEL 0.16, CADD 23.30, Uncertain significance, not specified; Familial hemophagocytic lymphohistiocytosis 3
- L5F (p.Leu5Phe), cosmic curated COSV10722, gnomAD rs1221130860
- L5P (p.Leu5Pro), gnomAD rs1322153234, REVEL 0.34, CADD 17.00
- S6F (p.Ser6Phe), rs2143904920, ClinGen CA401120588, ClinVar RCV001951699, Ensembl rs2143904920, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- H7Y (p.His7Tyr), TOPMed rs2064971229, REVEL 0.08, CADD 8.88
- P8L (p.Pro8Leu), rs766811197, ClinGen CA8773699, ClinVar RCV001124308, ExAC rs766811197, REVEL 0.21, CADD 15.20, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- Q10H (p.Gln10His), rs1316667053, ClinGen CA401120483, ClinVar RCV001343071, TOPMed rs1316667053, REVEL 0.11, CADD 15.50, Uncertain significance, Inborn genetic diseases
- R11C (p.Arg11Cys), rs373721287, ClinGen CA8773697, cosmic curated COSV99256, ClinVar RCV002623270, REVEL 0.31, CADD 24.70, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R11H (p.Arg11His), rs574927621, ClinGen CA8773696, cosmic curated COSV10802, ClinVar RCV001963527, REVEL 0.20, CADD 24.50, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R11P (p.Arg11Pro), rs574927621, ClinGen CA8773695, NCI-TCGA Cosmic COSV5288, cosmic curated COSV52884, REVEL 0.35, CADD 24.90, Uncertain significance, not specified; Familial hemophagocytic lymphohistiocytosis 3
- F14L (p.Phe14Leu), ExAC rs776563028, TOPMed rs776563028, gnomAD rs776563028, REVEL 0.06, CADD 15.40, Likely benign
- L15F (p.Leu15Phe), gnomAD rs1468315530, REVEL 0.12, CADD 18.00
- L15V (p.Leu15Val), rs886053424, ClinGen CA10640599, ClinVar RCV000283703, Ensembl rs886053424, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R16C (p.Arg16Cys), rs370709761, ClinGen CA8773693, ClinVar RCV003322383, ClinVar RCV004334066, REVEL 0.37, CADD 26.20, Uncertain significance, not specified; Inborn genetic diseases
- R16G (p.Arg16Gly), rs370709761, ClinGen CA401120387, ClinVar RCV001936222, ESP rs370709761, REVEL 0.30, CADD 25.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R16H (p.Arg16His), rs149195431, ClinGen CA8773692, ClinVar RCV001965491, ClinVar RCV003222369, REVEL 0.27, CADD 24.60, Uncertain significance, not provided; Familial hemophagocytic lymphohistiocytosis 3
- Q17* (p.Gln17Ter), rs2064970978, ClinGen CA401120370, ClinVar RCV001248651, TOPMed rs2064970978, Pathogenic
- Q17E (p.Gln17Glu), TOPMed rs2064970978, Pathogenic
- Q17K (p.Gln17Lys), TOPMed rs2064970978, REVEL 0.14, CADD 23.80, Pathogenic
- K20E (p.Lys20Glu), TOPMed rs2064970921, REVEL 0.27, CADD 27.40
- K20Q (p.Lys20Gln), TOPMed rs2064970921
- K20R (p.Lys20Arg), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52883, Variant assessed as somatic; moderate impact.
- I21V (p.Ile21Val), ExAC rs778708063, TOPMed rs778708063, gnomAD rs778708063, REVEL 0.10, CADD 24.00
- R23C (p.Arg23Cys), rs575632298, ClinGen CA294091606, ClinVar RCV002035724, ClinVar RCV006396861, REVEL 0.25, CADD 29.20, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; Inborn genetic diseases
- R23H (p.Arg23His), rs554971343, ClinGen CA8773689, NCI-TCGA Cosmic COSV9925, cosmic curated COSV99257, REVEL 0.07, CADD 23.20, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; not specified
- R23L (p.Arg23Leu), rs554971343, ClinGen CA401120229, ClinVar RCV003092810, REVEL 0.16, CADD 23.30, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R24C (p.Arg24Cys), ExAC rs749234163, TOPMed rs749234163, gnomAD rs749234163, REVEL 0.27, CADD 27.20, Uncertain significance, Inborn genetic diseases
- R24G (p.Arg24Gly), rs749234163, ClinGen CA294091602, ClinVar RCV001959813, ClinVar RCV004793624, REVEL 0.21, CADD 22.60, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; not provided
- R24H (p.Arg24His), rs777619516, ClinGen CA8773687, cosmic curated COSV52886, ClinVar RCV000688781, REVEL 0.17, CADD 22.60, Uncertain significance, not provided; Familial hemophagocytic lymphohistiocytosis 3
- R24S (p.Arg24Ser), rs749234163, ClinGen CA401120223, cosmic curated COSV10875, ClinVar RCV000640095, REVEL 0.15, CADD 23.50, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R25K (p.Arg25Lys), TOPMed rs1013790378, REVEL 0.07, CADD 6.70, Uncertain significance
- R25T (p.Arg25Thr), rs1013790378, ClinGen CA401120208, ClinVar RCV001208326, TOPMed rs1013790378, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- V26I (p.Val26Ile), TOPMed rs2064970692
- D28V (p.Asp28Val), ExAC rs756041281, gnomAD rs756041281, REVEL 0.22, CADD 23.00
- L29V (p.Leu29Val), gnomAD rs2064970609, REVEL 0.07, CADD 11.10
- Q30* (p.Gln30Ter), ExAC rs780543569, gnomAD rs780543569, CADD 37.00
- Q30H (p.Gln30His), gnomAD rs1216024873, REVEL 0.16, CADD 22.10
- D31E (p.Asp31Glu), ExAC rs754691045, TOPMed rs754691045, gnomAD rs754691045, REVEL 0.06, CADD 11.60, Uncertain significance, Inborn genetic diseases
- D31N (p.Asp31Asn), rs2545989666, ClinGen CA401120134, ClinVar RCV002599892, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- P32H (p.Pro32His), ExAC rs766863447, TOPMed rs766863447, gnomAD rs766863447, REVEL 0.14, CADD 23.60
- P32L (p.Pro32Leu), rs766863447, NCI-TCGA Cosmic COSV5288, cosmic curated COSV52885, ExAC rs766863447, REVEL 0.11, CADD 19.90, Variant assessed as somatic; moderate impact.
- P32S (p.Pro32Ser), Ensembl rs1403410014, REVEL 0.11, CADD 15.50
- P33L (p.Pro33Leu), rs140437526, ClinGen CA8773679, cosmic curated COSV10956, ClinVar RCV001373712, REVEL 0.09, CADD 2.79, Conflicting interpretations, Inborn genetic diseases; not provided; Familial hemophagocytic lymphohistiocytos
- P33Q (p.Pro33Gln), rs140437526, ClinGen CA8773680, ClinVar RCV002608897, 1000Genomes rs140437526, REVEL 0.09, CADD 1.28, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- M36K (p.Met36Lys), ExAC rs762206310, gnomAD rs762206310, REVEL 0.16, CADD 0.01
- M36V (p.Met36Val), gnomAD rs1358667977, REVEL 0.05, CADD 6.56
- A37V (p.Ala37Val), gnomAD rs1411928994, REVEL 0.06, CADD 10.70
- P38L (p.Pro38Leu), rs202020609, ClinGen CA8773672, ClinVar RCV001071938, 1000Genomes rs202020609, REVEL 0.05, CADD 4.61, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- P38R (p.Pro38Arg), rs202020609, ClinGen CA8773671, ClinVar RCV001512833, 1000Genomes rs202020609, REVEL 0.04, CADD 4.26, Benign, Familial hemophagocytic lymphohistiocytosis 3
- E39G (p.Glu39Gly), TOPMed rs2064970175
- E39V (p.Glu39Val), TOPMed rs2064970175, REVEL 0.17, CADD 32.00
- I40=, rs1462217837, NCI-TCGA Cosmic COSV9925, Variant assessed as somatic; low impact.
- I40F (p.Ile40Phe), ExAC rs760660823, gnomAD rs760660823
- I40L (p.Ile40Leu), ExAC rs760660823, gnomAD rs760660823, REVEL 0.05, CADD 12.10
- I40T (p.Ile40Thr), TOPMed rs2064964540, REVEL 0.06, CADD 10.20
- P43L (p.Pro43Leu), rs1167822487, gnomAD rs1167822487, REVEL 0.04, CADD 18.40, Variant assessed as somatic; moderate impact.
- P43S (p.Pro43Ser), ExAC rs775174271, gnomAD rs775174271, REVEL 0.08, CADD 9.76
- H45Y (p.His45Tyr), TOPMed rs2064964449, REVEL 0.08, CADD 21.50
- H46N (p.His46Asn), 1000Genomes rs145293891, ESP rs145293891, ExAC rs145293891, TOPMed rs145293891, REVEL 0.15, CADD 18.90
- H46R (p.His46Arg), TOPMed rs1321057434, gnomAD rs1321057434, REVEL 0.14, CADD 14.40
- F47L (p.Phe47Leu), ExAC rs745527375, gnomAD rs745527375, REVEL 0.06, CADD 6.11
- S48C (p.Ser48Cys), TOPMed rs1349079353, REVEL 0.19, CADD 23.50
- S48F (p.Ser48Phe), TOPMed rs1349079353, REVEL 0.15, CADD 22.00
- P49H (p.Pro49His), ExAC rs778358863, gnomAD rs778358863
- P49L (p.Pro49Leu), cosmic curated COSV52883, ExAC rs778358863, gnomAD rs778358863
- E50* (p.Glu50Ter), rs756652448, ClinGen CA401118030, ClinVar RCV003604237, Pathogenic
- E50A (p.Glu50Ala), TOPMed rs2064964284
- E50D (p.Glu50Asp), TOPMed rs2064964269
- E50K (p.Glu50Lys), ExAC rs756652448, REVEL 0.12, CADD 13.50, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- E50Q (p.Glu50Gln), ExAC rs756652448, REVEL 0.07, CADD 11.70, Uncertain significance, Inborn genetic diseases
- E50S (p.Glu50Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q51* (p.Gln51Ter), rs2545988497, ClinGen CA401117994, ClinVar RCV003498095, Pathogenic
- Q51H (p.Gln51His), ESP rs139726111, ExAC rs139726111, TOPMed rs139726111, gnomAD rs139726111, REVEL 0.09, CADD 33.00
- R52Q (p.Arg52Gln), rs750613531, ClinGen CA8773595, NCI-TCGA Cosmic COSV5288, cosmic curated COSV52885, REVEL 0.06, CADD 24.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R52W (p.Arg52Trp), rs930596937, ClinGen CA294090247, ClinVar RCV002720160, TOPMed rs930596937, REVEL 0.14, CADD 32.00, Uncertain significance, Inborn genetic diseases; Familial hemophagocytic lymphohistiocytosis 3
- L54C (p.Leu54Cys), rs1363960054, ClinGen CA627596929, ClinVar RCV003604963, Pathogenic
- L55F (p.Leu55Phe), ExAC rs760475083, gnomAD rs760475083, REVEL 0.62, CADD 24.30
- L55P (p.Leu55Pro), TOPMed rs1205701179, gnomAD rs1205701179
- E57A (p.Glu57Ala), gnomAD rs1323557147
- E57K (p.Glu57Lys), rs767617631, ClinGen CA8773591, cosmic curated COSV10956, ClinVar RCV001038916, REVEL 0.16, CADD 22.40, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- D58G (p.Asp58Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D58N (p.Asp58Asn), Ensembl rs1567822588
- A59P (p.Ala59Pro), 1000Genomes rs9904366, ESP rs9904366, ExAC rs9904366, TOPMed rs9904366, REVEL 0.48, CADD 21.70, Benign
- A59S (p.Ala59Ser), 1000Genomes rs9904366, ESP rs9904366, ExAC rs9904366, TOPMed rs9904366, Benign
- A59T (p.Ala59Thr), rs9904366, ClinGen CA8773587, cosmic curated COSV52884, ClinVar RCV000252059, REVEL 0.07, CADD 16.60, Conflicting interpretations, Autoinflammatory syndrome; not specified; not provided
- L60F (p.Leu60Phe), rs2545988116, ClinGen CA401117530, ClinVar RCV003041031, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- Y61H (p.Tyr61His), rs2143901173, ClinGen CA401117498, ClinVar RCV001991422, Ensembl rs2143901173, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- T62I (p.Thr62Ile), rs1567822572, ClinGen CA401117432, cosmic curated COSV52886, ClinVar RCV004481919, REVEL 0.56, CADD 24.70, Uncertain significance, Inborn genetic diseases
- H65Q (p.His65Gln), TOPMed rs1036402374, REVEL 0.30, CADD 24.30
- H65Y (p.His65Tyr), gnomAD rs1383311404, REVEL 0.07, CADD 17.80
- R66C (p.Arg66Cys), rs996214730, ClinGen CA294090223, ClinVar RCV001909827, TOPMed rs996214730, REVEL 0.58, CADD 31.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R66H (p.Arg66His), rs371943727, ClinGen CA8773586, ClinVar RCV001305031, ClinVar RCV004692457, REVEL 0.52, CADD 27.30, Uncertain significance, not provided; Familial hemophagocytic lymphohistiocytosis 3
- R66L (p.Arg66Leu), rs371943727, ClinGen CA10650176, ClinVar RCV000371614, ClinVar RCV006386808, REVEL 0.59, CADD 27.00, Uncertain significance, Inborn genetic diseases; Familial hemophagocytic lymphohistiocytosis 3
- R66P (p.Arg66Pro), ESP rs371943727, ExAC rs371943727, TOPMed rs371943727, gnomAD rs371943727, REVEL 0.61, CADD 29.50, Uncertain significance
- G68C (p.Gly68Cys), Ensembl rs2064961883, REVEL 0.82, CADD 27.10, Uncertain significance
- G68S (p.Gly68Ser), rs2064961883, ClinGen CA401117273, ClinVar RCV002814450, Ensembl rs2064961883, REVEL 0.68, CADD 26.20, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- H69Q (p.His69Gln), Ensembl rs2143901055
- H69R (p.His69Arg), TOPMed rs1249649287, gnomAD rs1249649287, REVEL 0.07, CADD 16.20
- H69Y (p.His69Tyr), rs748571320, ExAC rs748571320, TOPMed rs748571320, gnomAD rs748571320, REVEL 0.05, CADD 20.80, Uncertain significance, Inborn genetic diseases
- N73T (p.Asn73Thr), Ensembl rs1599415503
- H74Q (p.His74Gln), TOPMed rs1599415501, gnomAD rs1599415501, Likely benign
- T76M (p.Thr76Met), rs78028658, ClinGen CA8773582, cosmic curated COSV52886, ClinVar RCV000640097, REVEL 0.17, CADD 4.91, Conflicting interpretations, not specified; not provided; Familial hemophagocytic lymphohistiocytosis 3
- A78V (p.Ala78Val), ExAC rs758450528, TOPMed rs758450528, gnomAD rs758450528, REVEL 0.04, CADD 18.50
- S79F (p.Ser79Phe), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52884, Variant assessed as somatic; moderate impact.
- E80K (p.Glu80Lys), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52883, Variant assessed as somatic; moderate impact.
- R83* (p.Arg83Ter), rs1274685768, ClinGen CA401116746, NCI-TCGA Cosmic COSV5288, cosmic curated COSV52882, CADD 35.00, Pathogenic
- R83P (p.Arg83Pro), ESP rs143944122, ExAC rs143944122, TOPMed rs143944122, gnomAD rs143944122, REVEL 0.09, CADD 3.87, Uncertain significance
- R83Q (p.Arg83Gln), rs143944122, ClinGen CA8773577, cosmic curated COSV10503, ClinVar RCV000809917, REVEL 0.02, CADD 0.44, Uncertain significance, not provided; Familial hemophagocytic lymphohistiocytosis 3
- Y84* (p.Tyr84Ter), rs2545988044, ClinGen CA401116678, ClinVar RCV003604314, CADD 36.00, Pathogenic
- Y84H (p.Tyr84His), Ensembl rs2064961564
- Q86* (p.Gln86Ter), gnomAD rs1296057331, CADD 41.00
- Q86R (p.Gln86Arg), Ensembl rs2143900860
- E87K (p.Glu87Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A88T (p.Ala88Thr), cosmic curated COSV10454, ExAC rs749977344, gnomAD rs749977344, REVEL 0.30, CADD 32.00
- H90Q (p.His90Gln), ExAC rs761478169, TOPMed rs761478169, gnomAD rs761478169, REVEL 0.03, CADD 6.97, Likely benign
- H90R (p.His90Arg), ExAC rs764690495, gnomAD rs764690495
- V91A (p.Val91Ala), Ensembl rs908100538
- V91M (p.Val91Met), rs374308904, ClinGen CA8773546, cosmic curated COSV99256, ClinVar RCV000224157, REVEL 0.04, CADD 0.04, Conflicting interpretations, UNC13D-related disorder; Inborn genetic diseases; not provided
- E92G (p.Glu92Gly), Ensembl rs1599415335
- P93T (p.Pro93Thr), rs137882090, ClinGen CA8773544, ClinVar RCV003073307, ClinVar RCV005774547, REVEL 0.15, CADD 18.10, Uncertain significance, Inborn genetic diseases; Familial hemophagocytic lymphohistiocytosis 3
- E94D (p.Glu94Asp), TOPMed rs2064960363, gnomAD rs2064960363, REVEL 0.02, CADD 13.30
- E94K (p.Glu94Lys), rs537781874, ClinGen CA8773541, ClinVar RCV001050153, ClinVar RCV005286287, REVEL 0.12, CADD 6.97, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; Inborn genetic diseases
- E95K (p.Glu95Lys), cosmic curated COSV10722, TOPMed rs1474069422, gnomAD rs1474069422, REVEL 0.06, CADD 23.00
- H96Q (p.His96Gln), rs2545987898, ClinGen CA401116053, ClinVar RCV003034855, REVEL 0.17, CADD 22.80, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- H96Y (p.His96Tyr), rs774601988, ClinGen CA8773540, ClinVar RCV002890877, ClinVar RCV004966147, REVEL 0.29, CADD 24.70, Uncertain significance, Inborn genetic diseases; Familial hemophagocytic lymphohistiocytosis 3
- Q97R (p.Gln97Arg), 1000Genomes rs200891884, REVEL 0.08, CADD 1.73
- T99I (p.Thr99Ile), rs2545987881, ClinGen CA401115951, ClinVar RCV003027206, REVEL 0.05, CADD 0.12, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- Q101R (p.Gln101Arg), rs1280197502, ClinGen CA401115914, ClinVar RCV000801840, gnomAD rs1280197502, REVEL 0.02, CADD 14.40, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R102Q (p.Arg102Gln), rs778208597, ClinGen CA8773535, NCI-TCGA Cosmic COSV9925, cosmic curated COSV99257, REVEL 0.02, CADD 9.27, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- R102W (p.Arg102Trp), rs749533827, ClinGen CA8773536, ClinVar RCV000822629, ClinVar RCV005772037, REVEL 0.08, CADD 21.80, Uncertain significance, Inborn genetic diseases; not provided; Familial hemophagocytic lymphohistiocytos
- V103I (p.Val103Ile), TOPMed rs1185941307, gnomAD rs1185941307, REVEL 0.08, CADD 20.30
- V103S (p.Val103Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R104G (p.Arg104Gly), TOPMed rs1370559593, gnomAD rs1370559593, REVEL 0.06, CADD 14.70
- R104M (p.Arg104Met), cosmic curated COSV10583, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E105K (p.Glu105Lys), NCI-TCGA TCGA novel, REVEL 0.03, CADD 14.90, Variant assessed as somatic; moderate impact.
- K108R (p.Lys108Arg), rs2064959179, ClinGen CA401115661, ClinVar RCV001049905, Ensembl rs2064959179, REVEL 0.06, CADD 22.50, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- I110V (p.Ile110Val), rs547919091, ClinGen CA8773514, ClinVar RCV001304797, ClinVar RCV002543112, REVEL 0.01, CADD 3.88, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; Inborn genetic diseases
- C112L (p.Cys112Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- C112R (p.Cys112Arg), rs771709162, ClinGen CA8773513, ClinVar RCV001209487, ExAC rs771709162, REVEL 0.23, CADD 32.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- C112S (p.Cys112Ser), rs141540493, ClinGen CA8773512, ClinVar RCV001037027, ClinVar RCV002222659, REVEL 0.17, CADD 23.50, Uncertain significance, not specified; Familial hemophagocytic lymphohistiocytosis 3
- C112Y (p.Cys112Tyr), ESP rs141540493, ExAC rs141540493, TOPMed rs141540493, gnomAD rs141540493, REVEL 0.17, CADD 25.70, Uncertain significance
- K114T (p.Lys114Thr), TOPMed rs2064959047, gnomAD rs2064959047, REVEL 0.42, CADD 28.00
- A115T (p.Ala115Thr), TOPMed rs1267574358, gnomAD rs1267574358, REVEL 0.20, CADD 26.50
- T116I (p.Thr116Ile), TOPMed rs2064959011, gnomAD rs2064959011, REVEL 0.60, CADD 32.00
- T116R (p.Thr116Arg), TOPMed rs2064959011, gnomAD rs2064959011
- K121R (p.Lys121Arg), ExAC rs757169382, gnomAD rs757169382
- G122D (p.Gly122Asp), TOPMed rs2064958965
- G125A (p.Gly125Ala), gnomAD rs2064958929, NCI-TCGA TCGA novel, REVEL 0.23, CADD 23.80, Variant assessed as somatic; high impact.
- D127H (p.Asp127His), Ensembl rs2064958913
- V128I (p.Val128Ile), TOPMed rs2064958897
- S129G (p.Ser129Gly), ExAC rs777113713, gnomAD rs777113713, REVEL 0.24, CADD 27.20
- G130E (p.Gly130Glu), rs747840374, ClinGen CA8773489, ClinVar RCV002701020, ClinVar RCV003167647, REVEL 0.51, CADD 31.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3; Inborn genetic diseases
- F131L (p.Phe131Leu), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52884, REVEL 0.12, CADD 22.90, Variant assessed as somatic; moderate impact.
- D133A (p.Asp133Ala), gnomAD rs1599414903
- D133N (p.Asp133Asn), rs534150507, ClinGen CA8773487, ClinVar RCV002572237, 1000Genomes rs534150507, REVEL 0.57, CADD 29.70, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- P134R (p.Pro134Arg), ExAC rs752011807, gnomAD rs752011807, REVEL 0.93, CADD 31.00
- Y135F (p.Tyr135Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C136F (p.Cys136Phe), gnomAD rs1188800286, REVEL 0.66, CADD 29.40
- C136S (p.Cys136Ser), TOPMed rs2064957114
- C136Y (p.Cys136Tyr), gnomAD rs1188800286
- L137V (p.Leu137Val), ExAC rs766811211, gnomAD rs766811211, REVEL 0.18, CADD 23.90
- L138M (p.Leu138Met), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52887, Variant assessed as somatic; moderate impact.
- G139A (p.Gly139Ala), TOPMed rs913613570, gnomAD rs913613570
- G139V (p.Gly139Val), TOPMed rs913613570, gnomAD rs913613570, REVEL 0.22, CADD 23.20
- I140T (p.Ile140Thr), rs1181554837, ClinGen CA401114579, ClinVar RCV001313913, TOPMed rs1181554837, REVEL 0.84, CADD 27.00, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- E141Q (p.Glu141Gln), NCI-TCGA Cosmic COSV5288, cosmic curated COSV52886, Variant assessed as somatic; moderate impact.
- Q142H (p.Gln142His), Ensembl rs2064956987, REVEL 0.07, CADD 13.30
- G143E (p.Gly143Glu), TOPMed rs1482742104
- V144I (p.Val144Ile), TOPMed rs987855651, gnomAD rs987855651, REVEL 0.01, CADD 6.41, Uncertain significance
- V144L (p.Val144Leu), rs987855651, ClinGen CA401114522, ClinVar RCV001875612, TOPMed rs987855651, Uncertain significance, Familial hemophagocytic lymphohistiocytosis 3
- G145A (p.Gly145Ala), rs571794057, ClinGen CA8773484, ClinVar RCV003196113, 1000Genomes rs571794057, REVEL 0.09, CADD 7.88, Uncertain significance, Inborn genetic diseases
- P147A (p.Pro147Ala), gnomAD rs2064956888, REVEL 0.05, CADD 4.30
- G148A (p.Gly148Ala), rs551855408, ClinGen CA8773483, ClinVar RCV001949098, ClinVar RCV002562174, REVEL 0.03, CADD 2.37, Uncertain significance, Inborn genetic diseases; Familial hemophagocytic lymphohistiocytosis 3
- G148E (p.Gly148Glu), cosmic curated COSV10633, 1000Genomes rs551855408, ExAC rs551855408, TOPMed rs551855408, Uncertain significance
- G148V (p.Gly148Val), 1000Genomes rs551855408, ExAC rs551855408, TOPMed rs551855408, gnomAD rs551855408, Uncertain significance
- G149A (p.Gly149Ala), rs2064956872, ClinGen CA502050608, ClinVar RCV003050492, Pathogenic
- G149S (p.Gly149Ser), ExAC rs761868892, TOPMed rs761868892, gnomAD rs761868892, REVEL 0.07, CADD 13.50
- S150N (p.Ser150Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S150Q (p.Ser150Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S150R (p.Ser150Arg), TOPMed rs1442743528, gnomAD rs1442743528, REVEL 0.06, CADD 15.70
Public UNC13D analysis runs
- UNC13D analysis run — UNC13D (1,629 variants) — completed 2026-08-22