AGRN (Agrin) variants and mutations
AGRN (also known as Agrin) is a human protein-coding gene encoding an agrin protein. At the neuromuscular junction, it organizes postsynaptic differentiation by activating the LRP4-MuSK signaling pathway and clustering acetylcholine receptors. Biallelic or dominant pathogenic variants can cause congenital myasthenic syndromes with fatigable muscle weakness. This analysis covers 107 AGRN variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes congenital myasthenic syndrome 8, Congenital myasthenic syndromes, and Postsynaptic congenital myasthenic syndromes. Example AGRN variants include A2S, A2T, and A2P.
Variant analysis overview
- Gene: AGRN
- Protein: Agrin
- UniProt accession: O00468
- Organism: Homo sapiens
- Variants analyzed: 107
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 26 unspecified-consequence records; 1 natural variant; 57 missense variants; 13 synonymous variants; 5 frameshift variants; 2 in-frame deletions; 3 substitution
- Prediction scores: 104 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: congenital myasthenic syndrome 8, Congenital myasthenic syndromes, Postsynaptic congenital myasthenic syndromes, Presynaptic congenital myasthenic syndromes, COVID-19, fetal akinesia deformation sequence, dengue disease, presynaptic congenital myasthenic syndrome, neurodevelopmental disorder, postsynaptic congenital myasthenic syndrome, Abnormality of the musculature, congenital myasthenic syndrome.
Protein structure and variant hotspots
- Protein features: 20 domains; 4 binding sites; 7 post-translational modification sites.
- Structural context: 23 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable AGRN variants
Examples include A2S, A2T, A2P, A2V, A2G, A2D, A2A, G3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), gnomAD 1-1020176-G-T, REVEL 0.21, MetaLR 0.23
- A2T (p.Ala2Thr), rs1394080131, gnomAD 1-1020176-G-A, REVEL 0.24, MetaLR 0.26
- A2P (p.Ala2Pro), rs1394080131, gnomAD 1-1020176-G-C, REVEL 0.26, MetaLR 0.22
- A2V (p.Ala2Val), gnomAD 1-1020177-C-T, REVEL 0.14, MetaLR 0.21
- A2G (p.Ala2Gly), gnomAD 1-1020177-C-G, REVEL 0.21, MetaLR 0.21
- A2D (p.Ala2Asp), rs776698665, gnomAD 1-1020177-C-A, REVEL 0.17, MetaLR 0.24
- A2A (p.Ala2Ala), gnomAD 1-1020178-C-A, CADD 12.70
- G3S (p.Gly3Ser), rs1329485459, gnomAD 1-1020179-G-A, REVEL 0.10, MetaLR 0.19
- G3R (p.Gly3Arg), rs1329485459, gnomAD 1-1020179-G-C, REVEL 0.14, MetaLR 0.17
- G3C (p.Gly3Cys), gnomAD 1-1020179-G-T, REVEL 0.17, MetaLR 0.25
- G3D (p.Gly3Asp), gnomAD 1-1020180-G-A, REVEL 0.14, MetaLR 0.31
- G3A (p.Gly3Ala), gnomAD 1-1020180-G-C, REVEL 0.16, MetaLR 0.28
- G3V (p.Gly3Val), gnomAD 1-1020180-G-T, REVEL 0.14, MetaLR 0.32
- G3G (p.Gly3Gly), gnomAD 1-1020181-C-A, CADD 6.63
- R4R (p.Arg4Arg), gnomAD 1-1020182-C-A, CADD 9.07
- R4W (p.Arg4Trp), rs1337682906, gnomAD 1-1020182-C-T, REVEL 0.18, MetaLR 0.22
- R4G (p.Arg4Gly), rs1337682906, gnomAD 1-1020182-C-G, REVEL 0.16, MetaLR 0.25
- R4L (p.Arg4Leu), rs539283387, gnomAD 1-1020183-G-T, REVEL 0.15, MetaLR 0.14
- R4Q (p.Arg4Gln), gnomAD 1-1020183-G-A, REVEL 0.12, MetaLR 0.21
- R4P (p.Arg4Pro), rs539283387, gnomAD 1-1020183-G-C, REVEL 0.13, MetaLR 0.20
- S5P (p.Ser5Pro), gnomAD 1-1020185-T-C, REVEL 0.11, MetaLR 0.26
- S5F (p.Ser5Phe), gnomAD 1-1020186-C-T, REVEL 0.15, MetaLR 0.31
- S5Y (p.Ser5Tyr), gnomAD 1-1020186-C-A, REVEL 0.10, MetaLR 0.32
- S5C (p.Ser5Cys), gnomAD 1-1020186-C-G, REVEL 0.14, MetaLR 0.26
- S5S (p.Ser5Ser), gnomAD 1-1020187-C-T, CADD 8.37
- H6T (p.His6Thr), gnomAD 1-1020185-TC-T, CADD 18.30
- H6P (p.His6Pro), gnomAD 1-1020188-CA-C, CADD 21.50
- H6N (p.His6Asn), gnomAD 1-1020188-C-A, REVEL 0.08, MetaLR 0.15
- H6Y (p.His6Tyr), gnomAD 1-1020188-C-T, REVEL 0.05, MetaLR 0.14
- H6R (p.His6Arg), rs1644363278, gnomAD 1-1020189-A-G, REVEL 0.08, MetaLR 0.12
- H6H (p.His6His), gnomAD 1-1020190-C-T, CADD 7.46
- H6Q (p.His6Gln), gnomAD 1-1020190-C-A, REVEL 0.19, MetaLR 0.19
- P7R (p.Pro7Arg), gnomAD 1-1020189-AC-A, CADD 21.20
- P7T (p.Pro7Thr), gnomAD 1-1020191-C-A, REVEL 0.15, MetaLR 0.30
- P7S (p.Pro7Ser), gnomAD 1-1020191-C-T, REVEL 0.16, MetaLR 0.28
- P7Q (p.Pro7Gln), gnomAD 1-1020192-C-A, REVEL 0.19, MetaLR 0.25
- P7L (p.Pro7Leu), rs1389840850, gnomAD 1-1020192-C-T, REVEL 0.19, MetaLR 0.25
- P7P (p.Pro7Pro), gnomAD 1-1020193-G-C, CADD 8.34
- G8S (p.Gly8Ser), gnomAD 1-1020194-G-A, REVEL 0.12, MetaLR 0.27
- G8C (p.Gly8Cys), gnomAD 1-1020194-G-T, REVEL 0.15, MetaLR 0.29
- G8D (p.Gly8Asp), gnomAD 1-1020195-G-A, REVEL 0.13, MetaLR 0.24
- G8A (p.Gly8Ala), gnomAD 1-1020195-G-C, REVEL 0.07, MetaLR 0.10
- G8V (p.Gly8Val), gnomAD 1-1020195-G-T, REVEL 0.14, MetaLR 0.24
- G8G (p.Gly8Gly), rs1317316964, gnomAD 1-1020196-C-T, CADD 8.64
- P9R (p.Pro9Arg), gnomAD 1-1020195-GC-G, CADD 19.40
- P9S (p.Pro9Ser), gnomAD 1-1020197-C-T, REVEL 0.24, MetaLR 0.20
- P9T (p.Pro9Thr), gnomAD 1-1020197-C-A, REVEL 0.18, MetaLR 0.18
- P9Q (p.Pro9Gln), gnomAD 1-1020198-C-A, REVEL 0.17, MetaLR 0.22
- P9L (p.Pro9Leu), gnomAD 1-1020198-C-T, REVEL 0.14, MetaLR 0.21
- P9P (p.Pro9Pro), gnomAD 1-1020199-G-T, CADD 11.50
- L10L (p.Leu10Leu), rs1226970553, gnomAD 1-1020200-C-T, CADD 12.10
- L10M (p.Leu10Met), rs1226970553, gnomAD 1-1020200-C-A, REVEL 0.22, MetaLR 0.34
- L10V (p.Leu10Val), gnomAD 1-1020200-C-G, REVEL 0.16, MetaLR 0.31
- L10P (p.Leu10Pro), gnomAD 1-1020201-T-C, REVEL 0.33, MetaLR 0.38
- L10Q (p.Leu10Gln), gnomAD 1-1020201-T-A, REVEL 0.33, MetaLR 0.31
- p.Arg11 Leu13del, gnomAD 1-1020194-GGCCCGC, CADD 15.50
- R11W (p.Arg11Trp), rs1481835054, gnomAD 1-1020203-C-T, REVEL 0.13, MetaLR 0.23
- R11R (p.Arg11Arg), gnomAD 1-1020203-C-A, CADD 12.40
- R11Q (p.Arg11Gln), gnomAD 1-1020204-G-A, REVEL 0.10, MetaLR 0.13
- R11L (p.Arg11Leu), rs1281912578, gnomAD 1-1020204-G-T, REVEL 0.12, MetaLR 0.12
- P12T (p.Pro12Thr), gnomAD 1-1020206-C-A, REVEL 0.07, MetaLR 0.26
- P12S (p.Pro12Ser), rs1224545239, gnomAD 1-1020206-C-T, REVEL 0.10, MetaLR 0.25
- P12L (p.Pro12Leu), gnomAD 1-1020207-C-T, REVEL 0.10, MetaLR 0.16
- P12Q (p.Pro12Gln), rs1460410228, gnomAD 1-1020207-C-A, REVEL 0.17, MetaLR 0.20
- P12P (p.Pro12Pro), rs1181200410, gnomAD 1-1020208-G-A, CADD 8.87
- L13M (p.Leu13Met), gnomAD 1-1020209-C-A, REVEL 0.17, MetaLR 0.26
- L13L (p.Leu13Leu), gnomAD 1-1020209-C-T, CADD 11.10
- L13P (p.Leu13Pro), rs1244520295, gnomAD 1-1020210-T-C, REVEL 0.12, MetaLR 0.25
- L14L (p.Leu14Leu), rs1306771410, gnomAD 1-1020212-C-T, CADD 11.20
- L14M (p.Leu14Met), gnomAD 1-1020212-C-A, REVEL 0.22, MetaLR 0.52
- L14Q (p.Leu14Gln), gnomAD 1-1020213-T-A, REVEL 0.29, MetaLR 0.51
- L14P (p.Leu14Pro), rs1423967880, gnomAD 1-1020213-T-C, REVEL 0.39, MetaLR 0.56
- p.Pro15 Leu17del, rs1196847979, gnomAD 1-1020204-GGCCGCT, CADD 18.90
- P15T (p.Pro15Thr), gnomAD 1-1020215-C-A, REVEL 0.07, MetaLR 0.16
- P15S (p.Pro15Ser), gnomAD 1-1020215-C-T, REVEL 0.09, MetaLR 0.14
- P15A (p.Pro15Ala), gnomAD 1-1020215-C-G, REVEL 0.08, MetaLR 0.15
- L16P (p.Leu16Pro), gnomAD 1-1020215-CCG-C, CADD 24.80
- V23L (p.Val23Leu), UniProt VAR 068724, REVEL 0.04, MetaLR 0.18, Conflicting interpretations, not specified; Congenital myasthenic syndrome 8; not provided
- D58N (p.Asp58Asn), UniProt VAR 068725, REVEL 0.27, MetaLR 0.13, Uncertain significance, Congenital myasthenic syndrome 8
- G76S (p.Gly76Ser), UniProt VAR 071367, REVEL 0.80, MetaLR 0.36, Pathogenic, Congenital myasthenic syndrome 8
- N105I (p.Asn105Ile), UniProt VAR 068726, MetaLR 0.15, MetaSVM -0.86, not provided, Congenital myasthenic syndrome
- P241S (p.Pro241Ser), rs879928015, Uncertain significance
- T267M (p.Thr267Met), UniProt VAR 068727, REVEL 0.27, MetaLR 0.56, Conflicting interpretations, Inborn genetic diseases; Congenital myasthenic syndrome 8; not provided
- A375S (p.Ala375Ser), rs138031468, UniProt VAR 068728, REVEL 0.27, MetaLR 0.32, Benign/Likely benign, Congenital myasthenic syndrome 8; not specified; not provided
- V554M (p.Val554Met), rs79016973, Likely benign / Benign
- E728V (p.Glu728Val), rs113288277, UniProt VAR 068729, REVEL 0.23, MetaLR 0.01, Benign, Congenital myasthenic syndrome 8; not specified; not provided
- A745V (p.Ala745Val), UniProt VAR 071368, REVEL 0.06, MetaLR 0.01
- Q852R (p.Gln852Arg), rs9697293, REVEL 0.04, MetaLR 0.00, Benign, not provided; Congenital myasthenic syndrome 8; not specified
- V984M (p.Val984Met), UniProt VAR 068731, REVEL 0.13, MetaLR 0.19, Uncertain significance, Congenital myasthenic syndrome 8; Inborn genetic diseases
- L1088F (p.Leu1088Phe), rs150132566, UniProt VAR 068732, REVEL 0.14, MetaLR 0.04, Uncertain significance, Congenital myasthenic syndrome 8; not specified; not provided
- T1118K (p.Thr1118Lys), rs149159118, UniProt VAR 068733, REVEL 0.45, MetaLR 0.50, Conflicting interpretations, Congenital myasthenic syndrome 8; not provided
- Q1135R (p.Gln1135Arg), rs142416636, UniProt VAR 068734, REVEL 0.19, MetaLR 0.07, Benign, Congenital myasthenic syndrome 8; not specified; not provided
- P1240L (p.Pro1240Leu), rs142620337, UniProt VAR 068735, REVEL 0.55, MetaLR 0.41, Conflicting interpretations, Congenital myasthenic syndrome 8; not specified; not provided
- G1341R (p.Gly1341Arg), UniProt VAR 068736, REVEL 0.77, MetaLR 0.90, Conflicting interpretations, Congenital myasthenic syndrome 8; not provided
- P1451L (p.Pro1451Leu), UniProt VAR 068737, REVEL 0.21, MetaLR 0.10, Benign/Likely benign, Congenital myasthenic syndrome 8; not specified; not provided
- A1514T (p.Ala1514Thr), rs111818381, UniProt VAR 068738, REVEL 0.12, MetaLR 0.09, Benign/Likely benign, Congenital myasthenic syndrome 8; not provided; not specified
- Q1565H (p.Gln1565His), rs199876002, UniProt VAR 068739, REVEL 0.29, MetaLR 0.31, Benign/Likely benign, not specified; Congenital myasthenic syndrome 8; not provided
- V1666I (p.Val1666Ile), rs17160775, UniProt VAR 048966, REVEL 0.19, MetaLR 0.00, Benign, Congenital myasthenic syndrome 8; not specified; not provided
- R1671Q (p.Arg1671Gln), UniProt VAR 068740, REVEL 0.24, MetaLR 0.19, Conflicting interpretations, Inborn genetic diseases; Congenital myasthenic syndrome 8
- R1698P (p.Arg1698Pro), UniProt VAR 068741, MetaLR 0.15, MetaSVM -0.93
- G1709R (p.Gly1709Arg), UniProt VAR 068742, REVEL 0.88, MetaLR 0.70, Pathogenic, Congenital myasthenic syndrome 8
- V1727F (p.Val1727Phe), UniProt VAR 069066, REVEL 0.84, MetaLR 0.81, Pathogenic, Congenital myasthenic syndrome 8
- R1734H (p.Arg1734His), rs145444272, UniProt VAR 068743, REVEL 0.76, MetaLR 0.58, Benign/Likely benign, Congenital myasthenic syndrome 8; not specified; not provided
- D1789N (p.Asp1789Asn), UniProt VAR 068744, MetaLR 0.52, MetaSVM -0.02, Conflicting interpretations, Congenital myasthenic syndrome 8; not specified; not provided
- G1875R (p.Gly1875Arg), UniProt VAR 071369, MetaLR 0.12, MetaSVM -0.95, Uncertain significance, Congenital myasthenic syndrome 8
- G2046V (p.Gly2046Val), UniProt VAR 068745, Uncertain significance, not provided; Inborn genetic diseases; Congenital myasthenic syndrome 8
Public AGRN analysis runs
- AGRN analysis run — AGRN (107 variants) — completed 2026-08-22