DYSF (Dysferlin) variants and mutations
DYSF (also known as Dysferlin) is a human protein-coding gene encoding a dysferlin protein. It is required for calcium-dependent membrane repair in skeletal muscle and contributes to vesicle fusion after sarcolemmal injury. Biallelic loss-of-function variants cause dysferlinopathies, including limb-girdle muscular dystrophy R2 and Miyoshi distal myopathy. This analysis covers 3,623 DYSF variants and mutations. Of these, 38% have computational variant effect predictions. Disease context includes autosomal recessive limb-girdle muscular dystrophy type 2B, Miyoshi muscular dystrophy 1, and distal myopathy with anterior tibial onset. Example DYSF variants include M1?, M1T, and M1V.
Variant analysis overview
- Gene: DYSF
- Protein: Dysferlin
- UniProt accession: O75923
- Organism: Homo sapiens
- Variants analyzed: 3623
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 3,487 unspecified-consequence records; 41 synonymous variants; 75 missense variants; 12 frameshift variants; 4 splice-region variants; 2 stop-gained variants; 3 substitution
- Prediction scores: 1,391 variants have prediction scores (38% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autosomal recessive limb-girdle muscular dystrophy type 2B, Miyoshi muscular dystrophy 1, distal myopathy with anterior tibial onset, autosomal recessive limb-girdle muscular dystrophy, Miyoshi myopathy, neuromuscular disease caused by qualitative or quantitative defects of dysferlin, Joubert syndrome and related disorders, Abnormality of the musculature, Distal lower limb muscle weakness, limb-girdle muscular dystrophy, congenital myopathy, Paradas type, muscular dystrophy.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 7 domains; 15 binding sites; 13 post-translational modification sites.
- Structural context: 1,638 variants have structural context.
- 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, MaveDB, LitVar.
Notable DYSF variants
Examples include M1?, M1T, M1V, L2P, L2R, L2L, L2M, R3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV50266
- M1T (p.Met1Thr), rs1459713589, ClinGen CA347205795, ClinVar RCV000668555, ClinVar RCV001377517, MetaLR 0.46, MetaSVM -0.05, Pathogenic
- M1V (p.Met1Val), rs1259378167, ClinGen CA347205786, ClinVar RCV000671280, MetaLR 0.45, MetaSVM -0.05, Likely pathogenic
- L2P (p.Leu2Pro), gnomAD rs1243373795, CADD 32.00
- L2R (p.Leu2Arg), cosmic curated COSV50512, CADD 31.00
- L2L (p.Leu2Leu), rs772536111, gnomAD 2-71454002-C-T, CADD 13.30
- L2M (p.Leu2Met), gnomAD 2-71466846-C-A, REVEL 0.53, CADD 26.50
- R3K (p.Arg3Lys), rs886043856, ClinGen CA10606034, ClinVar RCV000329343, TOPMed rs886043856, CADD 23.50, Uncertain significance
- R3S (p.Arg3Ser), rs2152620707, ClinGen CA347205848, ClinVar RCV003040143, CADD 22.70, Uncertain significance
- R3T (p.Arg3Thr), gnomAD 2-71454006-G-C, CADD 24.90
- R3R (p.Arg3Arg), rs2152620707, gnomAD 2-71454007-G-A, CADD 14.10
- R3G (p.Arg3Gly), rs2081568765, gnomAD 2-71466864-A-G, REVEL 0.16, CADD 23.20
- R3M (p.Arg3Met), gnomAD 2-71466865-G-T, REVEL 0.19, CADD 22.50
- V4G (p.Val4Gly), rs760262472, ClinGen CA1705169, ClinVar RCV002904598, ClinVar RCV003146674, CADD 29.40, Uncertain significance
- V4F (p.Val4Phe), gnomAD 2-71454008-G-T, CADD 26.90
- V4V (p.Val4Val), gnomAD 2-71454010-C-T, CADD 14.30
- V4M (p.Val4Met), rs2152643180, gnomAD 2-71466861-G-A, REVEL 0.17, CADD 22.70
- V4A (p.Val4Ala), gnomAD 2-71466862-T-C, REVEL 0.20, CADD 21.10
- I6N (p.Ile6Asn), rs1354334539, ClinGen CA347205929, ClinVar RCV000598153, ClinVar RCV001041107, CADD 29.20, Uncertain significance
- I6I (p.Ile6Ile), rs2080944093, gnomAD 2-71454016-C-T, CADD 15.20
- L7F (p.Leu7Phe), rs1373048381, ClinGen CA347205944, NCI-TCGA Cosmic COSV5057, cosmic curated COSV50572, CADD 23.10, Uncertain significance
- L7P (p.Leu7Pro), gnomAD rs2080944274, CADD 24.10
- L7S (p.Leu7Ser), gnomAD 2-71454015-TC-T, CADD 26.00
- L7L (p.Leu7Leu), rs2080944372, gnomAD 2-71454019-C-T, CADD 13.80
- L7V (p.Leu7Val), rs2081567899, gnomAD 2-71466855-C-G, REVEL 0.07, CADD 16.10
- L7R (p.Leu7Arg), gnomAD 2-71466859-T-G, REVEL 0.47, CADD 32.00
- Y8* (p.Tyr8Ter), rs2080944539, ClinGen CA347205987, ClinVar RCV001388527, ClinVar RCV001780363, CADD 34.00, Pathogenic
- Y8H (p.Tyr8His), gnomAD rs1227321624, CADD 22.90
- A9D (p.Ala9Asp), cosmic curated COSV10585
- A9S (p.Ala9Ser), gnomAD rs887165313, CADD 27.30, Uncertain significance
- A9T (p.Ala9Thr), rs887165313, ClinGen CA49734222, ClinVar RCV002634202, gnomAD rs887165313, REVEL 0.59, CADD 31.00, Uncertain significance
- A9A (p.Ala9Ala), rs771520271, gnomAD 2-71454025-C-G, CADD 4.84
- A9V (p.Ala9Val), gnomAD 2-71466868-C-T, REVEL 0.55, CADD 28.10
- A9E (p.Ala9Glu), gnomAD 2-71466886-C-A, REVEL 0.04, CADD 7.64
- E10D (p.Glu10Asp), TOPMed rs2080944921
- E10K (p.Glu10Lys), ExAC rs576699922, TOPMed rs576699922, gnomAD rs576699922, CADD 22.40
- E10E (p.Glu10Glu), gnomAD 2-71454028-G-A, CADD 12.70
- N11H (p.Asn11His), Ensembl rs1573205814
- N11K (p.Asn11Lys), rs760168438, ClinGen CA1705172, ClinVar RCV003146987, ExAC rs760168438, CADD 21.00, Uncertain significance
- N11S (p.Asn11Ser), TOPMed rs2080945073
- N11Y (p.Asn11Tyr), gnomAD 2-71454029-A-T, CADD 27.40
- N11N (p.Asn11Asn), gnomAD 2-71454031-C-T, CADD 8.57
- N11D (p.Asn11Asp), rs767584167, gnomAD 2-71466873-A-G, REVEL 0.32, CADD 24.40
- V12F (p.Val12Phe), rs2466863357, ClinGen CA347206070, ClinVar RCV003575138, Uncertain significance
- V12I (p.Val12Ile), cosmic curated COSV50274, CADD 19.90
- H13D (p.His13Asp), gnomAD 2-71454035-C-G, CADD 22.60
- H13R (p.His13Arg), gnomAD 2-71454036-A-G, CADD 14.80
- H13H (p.His13His), rs1005614411, gnomAD 2-71454037-C-T, CADD 12.70
- T14A (p.Thr14Ala), gnomAD 2-71454038-A-G, CADD 22.40
- T14T (p.Thr14Thr), rs1017462889, gnomAD 2-71454040-A-G, CADD 9.65
- P15A (p.Pro15Ala), ExAC rs755484132, TOPMed rs755484132, gnomAD rs755484132, CADD 15.80
- P15S (p.Pro15Ser), ExAC rs755484132, TOPMed rs755484132, gnomAD rs755484132, CADD 17.20
- P15L (p.Pro15Leu), gnomAD 2-71454042-C-T, CADD 19.60
- P15P (p.Pro15Pro), rs1305920372, gnomAD 2-71466881-C-T, CADD 14.80
- P15T (p.Pro15Thr), gnomAD 2-71466909-C-A, REVEL 0.47, CADD 23.80
- P15R (p.Pro15Arg), rs1387187109, gnomAD 2-71466910-C-G, REVEL 0.60, CADD 27.40
- D16H (p.Asp16His), rs140603487, ClinGen CA1705174, ClinVar RCV002942311, ClinVar RCV003146687, CADD 27.60, Likely benign
- D16N (p.Asp16Asn), ESP rs140603487, ExAC rs140603487, TOPMed rs140603487, gnomAD rs140603487, CADD 23.40, Likely benign
- T17A (p.Thr17Ala), rs2080945647, ClinGen CA347206207, ClinVar RCV002016294, TOPMed rs2080945647, CADD 4.12, Uncertain significance
- T17S (p.Thr17Ser), TOPMed rs1377182810, gnomAD rs1377182810, CADD 17.50
- T17T (p.Thr17Thr), rs763030202, gnomAD 2-71454049-C-T, CADD 14.00
- D18V (p.Asp18Val), gnomAD rs1227995661, CADD 31.00
- D18Y (p.Asp18Tyr), gnomAD 2-71454050-G-T, CADD 32.00
- D18N (p.Asp18Asn), gnomAD 2-71466894-G-A, REVEL 0.13, CADD 25.10
- D18G (p.Asp18Gly), rs750562195, gnomAD 2-71466895-A-G, REVEL 0.07, CADD 23.50
- D18E (p.Asp18Glu), gnomAD 2-71466896-C-A, REVEL 0.07, CADD 22.10
- I19F (p.Ile19Phe), gnomAD rs1259434756, CADD 23.10
- S20N (p.Ser20Asn), gnomAD rs1320882374, CADD 28.90
- S20T (p.Ser20Thr), rs1420619668, gnomAD 2-71454055-CAGCGA, CADD 32.00
- S20R (p.Ser20Arg), gnomAD 2-71454058-C-A, CADD 27.00
- S20S (p.Ser20Ser), gnomAD 2-71466872-C-T, CADD 16.00
- S20V (p.Ser20Val), rs1296020223, gnomAD 2-71466877-TC-T, CADD 22.40
- S20G (p.Ser20Gly), rs1317110085, gnomAD 2-71466882-A-G, REVEL 0.07, CADD 20.50
- S20I (p.Ser20Ile), gnomAD 2-71466883-G-T, REVEL 0.11, CADD 15.90
- D21H (p.Asp21His), NCI-TCGA Cosmic COSV5059, NCI-TCGA Cosmic COSV9924, cosmic curated COSV99249, Variant assessed as somatic; moderate impact.
- D21N (p.Asp21Asn), TOPMed rs1202468899, gnomAD rs1202468899, CADD 32.00
- D21Y (p.Asp21Tyr), cosmic curated COSV50592, TOPMed rs1202468899, gnomAD rs1202468899, CADD 32.00
- D21G (p.Asp21Gly), gnomAD 2-71454060-A-G, CADD 32.00
- D21V (p.Asp21Val), gnomAD 2-71466907-A-T, REVEL 0.84, CADD 29.70
- A22V (p.Ala22Val), ExAC rs764383398, gnomAD rs764383398
- A22A (p.Ala22Ala), gnomAD 2-71454064-C-T, CADD 15.60
- Y23C (p.Tyr23Cys), rs751600627, ClinGen CA1705177, ClinVar RCV003025292, ExAC rs751600627, CADD 31.00, Uncertain significance
- Y23H (p.Tyr23His), gnomAD 2-71454065-T-C, CADD 26.00
- Y23Y (p.Tyr23Tyr), gnomAD 2-71454067-C-T, CADD 14.40
- C24F (p.Cys24Phe), TOPMed rs2080946831, gnomAD rs2080946831, CADD 26.20
- C24Y (p.Cys24Tyr), TOPMed rs2080946831, gnomAD rs2080946831
- C24R (p.Cys24Arg), gnomAD 2-71454068-T-C, CADD 26.60
- C24S (p.Cys24Ser), gnomAD 2-71466849-TG-T, CADD 28.50
- C24G (p.Cys24Gly), gnomAD 2-71466849-T-G, REVEL 0.16, CADD 24.10
- C24C (p.Cys24Cys), gnomAD 2-71466851-C-T, CADD 15.60
- C24* (p.Cys24Ter), gnomAD 2-71466851-C-A, CADD 38.00
- C24W (p.Cys24Trp), gnomAD 2-71466854-C-G, REVEL 0.38, CADD 25.20
- S25F (p.Ser25Phe), cosmic curated COSV10804
- S25A (p.Ser25Ala), gnomAD 2-71454071-T-G, CADD 24.00
- S25Y (p.Ser25Tyr), gnomAD 2-71454072-C-A, CADD 25.90
- S25S (p.Ser25Ser), rs375772222, gnomAD 2-71454073-C-T, CADD 8.92
- S25T (p.Ser25Thr), rs1342818734, gnomAD 2-71466919-G-C, REVEL 0.11, CADD 23.50
- A26V (p.Ala26Val), cosmic curated COSV50447
- A26E (p.Ala26Glu), gnomAD 2-71454075-C-A, CADD 23.30
- A26A (p.Ala26Ala), rs1203786305, gnomAD 2-71454076-G-A, CADD 6.87
- A26S (p.Ala26Ser), gnomAD 2-71466915-G-T, REVEL 0.23, CADD 23.10
- A26T (p.Ala26Thr), rs1181790709, gnomAD 2-71466915-G-A, REVEL 0.16, CADD 23.10
- A26P (p.Ala26Pro), gnomAD 2-71466915-G-C, REVEL 0.48, CADD 25.70
- A26G (p.Ala26Gly), gnomAD 2-71466916-C-G, REVEL 0.33, CADD 23.50
- V27M (p.Val27Met), gnomAD rs1358539555, CADD 23.50
- V27V (p.Val27Val), gnomAD 2-71454079-G-C, CADD 14.20
- F28F (p.Phe28Phe), rs1261407949, gnomAD 2-71454082-T-C, CADD 16.50
- A29T (p.Ala29Thr), NCI-TCGA Cosmic COSV9924, cosmic curated COSV99249, CADD 23.70, Variant assessed as somatic; moderate impact.
- A29A (p.Ala29Ala), gnomAD 2-71454085-A-G, CADD 23.40
- G30=, NCI-TCGA Cosmic COSV9924, Variant assessed as somatic; low impact.
- G30E (p.Gly30Glu), gnomAD rs1380358087
- G30R (p.Gly30Arg), rs767637508, cosmic curated COSV10876, ClinGen CA1705179, ClinVar RCV001969563, CADD 35.00, Uncertain significance
- G30V (p.Gly30Val), gnomAD rs1380358087
- G30G (p.Gly30Gly), rs2152680463, gnomAD 2-71480884-G-C, CADD 12.60
- V31G (p.Val31Gly), cosmic curated COSV50400
- V31L (p.Val31Leu), ExAC rs752653599, TOPMed rs752653599, gnomAD rs752653599
- V31M (p.Val31Met), cosmic curated COSV50499, ExAC rs752653599, TOPMed rs752653599, gnomAD rs752653599
- K32M (p.Lys32Met), 1000Genomes rs539484245, ExAC rs539484245, TOPMed rs539484245, gnomAD rs539484245, Likely benign
- K32N (p.Lys32Asn), cosmic curated COSV99251, ExAC rs756910550, gnomAD rs756910550
- K32R (p.Lys32Arg), rs539484245, ClinGen CA1705219, cosmic curated COSV50276, ClinVar RCV001944403, AlphaMissense 0.91, MetaLR 0.43, Likely benign
- K32T (p.Lys32Thr), rs539484245, ClinGen CA1705218, ClinVar RCV001244563, ClinVar RCV001829933, AlphaMissense 0.91, MetaLR 0.43, Likely benign
- K32K (p.Lys32Lys), gnomAD 2-71466890-G-A, CADD 15.30
- K33T (p.Lys33Thr), rs539484245, gnomAD 2-71480889-A-C, REVEL 0.53, AlphaMissense 0.91
- K33R (p.Lys33Arg), rs539484245, gnomAD 2-71480889-A-G, REVEL 0.28, AlphaMissense 0.91
- K33M (p.Lys33Met), rs539484245, gnomAD 2-71480889-A-T, REVEL 0.69, AlphaMissense 0.91
- K33K (p.Lys33Lys), rs756910550, gnomAD 2-71480890-G-A, CADD 13.60
- K33N (p.Lys33Asn), rs756910550, gnomAD 2-71480890-G-C, REVEL 0.52, CADD 32.00
- R34I (p.Arg34Ile), NCI-TCGA TCGA novel, TOPMed rs2082827571, gnomAD rs2082827571, Variant assessed as somatic; moderate impact.
- R34R (p.Arg34Arg), gnomAD 2-71466897-C-A, CADD 15.70
- R34W (p.Arg34Trp), rs931174858, gnomAD 2-71466897-C-T, REVEL 0.31, CADD 25.30
- R34G (p.Arg34Gly), rs931174858, gnomAD 2-71466897-C-G, REVEL 0.07, CADD 22.60
- R34H (p.Arg34His), rs2081572094, gnomAD 2-71466901-G-A, REVEL 0.19, CADD 25.00
- R34* (p.Arg34Ter), gnomAD 2-71466930-C-T, CADD 43.00
- R34Q (p.Arg34Gln), gnomAD 2-71466931-G-A, REVEL 0.15, CADD 26.10
- R34L (p.Arg34Leu), gnomAD 2-71466931-G-T, REVEL 0.21, CADD 27.30
- R34K (p.Arg34Lys), gnomAD 2-71480895-G-A, REVEL 0.13, CADD 20.40
- T35A (p.Thr35Ala), rs985470984, TOPMed rs985470984, AlphaMissense 0.95, MetaLR 0.86, Uncertain significance
- T35S (p.Thr35Ser), rs985470984, ClinGen CA49750035, ClinVar RCV003146980, ClinVar RCV005824505, AlphaMissense 0.95, MetaLR 0.86, Uncertain significance
- T35K (p.Thr35Lys), gnomAD 2-71480893-G-GAGA, CADD 29.50
- T35I (p.Thr35Ile), gnomAD 2-71480898-C-T, REVEL 0.83, CADD 26.20
- T35T (p.Thr35Thr), rs749854198, gnomAD 2-71480899-C-T, CADD 9.41
- K36* (p.Lys36Ter), NCI-TCGA Cosmic COSV9924, cosmic curated COSV99249, Variant assessed as somatic; high impact.
- K36E (p.Lys36Glu), rs2082828360, ClinGen CA347215968, ClinVar RCV001295278, Ensembl rs2082828360, AlphaMissense 0.90, MetaLR 0.33, Uncertain significance
- K36N (p.Lys36Asn), TOPMed rs1316230143, gnomAD rs1316230143, NCI-TCGA TCGA novel, Likely benign
- K36R (p.Lys36Arg), TOPMed rs1376398023
- K36S (p.Lys36Ser), rs398123764, gnomAD 2-71480899-CAA-C, CADD 32.00
- V37I (p.Val37Ile), gnomAD rs1262804089
- V37V (p.Val37Val), rs963586500, gnomAD 2-71480905-C-T, CADD 12.10
- I38V (p.Ile38Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I38T (p.Ile38Thr), gnomAD 2-71480906-AT-A, CADD 32.00
- K39* (p.Lys39Ter), rs2082829594, ClinGen CA347216014, ClinVar RCV001264239, Ensembl rs2082829594, Likely pathogenic
- K39M (p.Lys39Met), ExAC rs779471597
- K39N (p.Lys39Asn), Ensembl rs2082829925, Likely benign
- K39R (p.Lys39Arg), gnomAD 2-71480910-A-G, REVEL 0.24, CADD 27.00
- N40S (p.Asn40Ser), ExAC rs749801723, gnomAD rs749801723
- N40Y (p.Asn40Tyr), rs911341473, ClinGen CA49750078, ClinVar RCV002043688, TOPMed rs911341473, AlphaMissense 0.68, MetaLR 0.59, Uncertain significance
- N40T (p.Asn40Thr), rs746833738, gnomAD 2-71480910-AG-A, CADD 32.00
- S41N (p.Ser41Asn), cosmic curated COSV50556
- S41R (p.Ser41Arg), cosmic curated COSV50450, ESP rs369755508, ExAC rs369755508, TOPMed rs369755508, Likely benign
- S41S (p.Ser41Ser), rs369755508, gnomAD 2-71480917-C-T, CADD 2.42
- V42G (p.Val42Gly), rs199772109, ClinGen CA49750141, ClinVar RCV003146933, gnomAD rs199772109, AlphaMissense 0.22, MetaLR 0.32, Uncertain significance
- V42M (p.Val42Met), rs374203339, ClinGen CA1705230, ClinVar RCV000536797, ClinVar RCV000711545, AlphaMissense 0.14, MetaLR 0.28, Uncertain significance
- V42L (p.Val42Leu), gnomAD 2-71480918-G-T, REVEL 0.12, CADD 17.00
- V42E (p.Val42Glu), gnomAD 2-71480919-T-A, REVEL 0.35, CADD 27.20
- N43K (p.Asn43Lys), rs772240035, ClinGen CA1705231, ClinVar RCV000596018, ClinVar RCV000814681, AlphaMissense 0.92, MetaLR 0.60, Likely benign
- N43T (p.Asn43Thr), rs1478546068, ClinGen CA347216068, ClinVar RCV002008001, TOPMed rs1478546068, AlphaMissense 0.61, MetaLR 0.59, Uncertain significance
- N43E (p.Asn43Glu), rs1573399606, gnomAD 2-71480918-G-GT, CADD 32.00
- N43D (p.Asn43Asp), gnomAD 2-71480921-A-G, REVEL 0.48, CADD 27.70
- N43S (p.Asn43Ser), gnomAD 2-71480922-A-G, REVEL 0.56, CADD 25.80
- N43N (p.Asn43Asn), rs772240035, gnomAD 2-71480923-C-T, AlphaMissense 0.92, MetaLR 0.60
- P44H (p.Pro44His), NCI-TCGA Cosmic COSV5044, NCI-TCGA Cosmic COSV5047, cosmic curated COSV50474, Variant assessed as somatic; moderate impact.
- P44L (p.Pro44Leu), rs773503180, ClinGen CA347216082, NCI-TCGA Cosmic COSV5044, cosmic curated COSV50448, AlphaMissense 0.97, MetaLR 0.94, Uncertain significance
- P44R (p.Pro44Arg), ExAC rs773503180, Uncertain significance
- P44P (p.Pro44Pro), rs886043852, gnomAD 2-71480926-T-C, CADD 3.45
- V45C (p.Val45Cys), rs1160607684, gnomAD 2-71480925-C-CT, CADD 32.00
- V45Y (p.Val45Tyr), gnomAD 2-71480925-CT-C, CADD 12.60
- V45L (p.Val45Leu), gnomAD 2-71480927-G-C, REVEL 0.32, CADD 24.10
- V45A (p.Val45Ala), gnomAD 2-71480928-T-C, REVEL 0.39, CADD 23.30
- V45V (p.Val45Val), gnomAD 2-71480929-A-G, CADD 8.75
- W46* (p.Trp46Ter), Ensembl rs2152680592
Public DYSF analysis runs
- DYSF analysis run — DYSF (3,623 variants) — completed 2026-08-21