# NM_004006.3(DMD):c.5724T>C (p.Asp1908=)

https://sugi.bio/variant/dmd-p-asp1908

## Summary

**DMD p.Asp1908= (c.5724T>C)** is classified **Benign/Likely benign** in DMD (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-03). Common (popmax 5.06%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Becker muscular dystrophy.

**At a glance:** Benign/Likely benign · review: Multiple submitters · rsID rs143159113 · 16 submitters · 4 linked conditions · common (popmax 5.06%, afr) — too common for a highly-penetrant pathogenic allele

## For patients & families {#patients}

This is a change in the DMD gene that is classified as benign/likely benign — not considered disease-causing, submitted by 16 submitters, and is linked to Becker muscular dystrophy.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | X-linked recessive |
| Age of onset (of this condition) | Adolescent, Adult, Childhood, Elderly |
| Prevalence | 1-9 / 100 000 (Europe) |
| Clinical trials | 74 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | DMD is a diagnostic-grade gene on 17 Genomics England panels |

**Commonly reported features of Becker muscular dystrophy** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Gait disturbance — Very frequent (99-80%)
- Myoglobinuria — Very frequent (99-80%)
- Elevated circulating creatine kinase concentration — Very frequent (99-80%)
- Myalgia — Very frequent (99-80%)
- Exercise intolerance — Very frequent (99-80%)
- Difficulty climbing stairs — Very frequent (99-80%)
- Abnormal urinary color — Very frequent (99-80%)
- Muscle weakness — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0005900/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DMD](https://sugi.bio/atlas/gene/DMD/) |
| Protein change (HGVS p.) | p.Asp1908= |
| Coding change (HGVS c.) | c.5724T>C |
| MANE Select transcript | [NM_004006](https://www.ncbi.nlm.nih.gov/nuccore/NM_004006) |
| dbSNP | [rs143159113](https://www.ncbi.nlm.nih.gov/snp/rs143159113/) |
| Variant type | single nucleotide variant |
| Location | chrX:32343149-32343149 (GRCh38) |
| ClinVar | [VCV94679](https://www.ncbi.nlm.nih.gov/clinvar/variation/94679/) |

**All HGVS expressions:** `LRG_199:g.1001461T>C`, `LRG_199t1:c.5724T>C`, `NC_000023.10:g.32361266A>G`, `NC_000023.11:g.32343149A>G`, `NG_012232.1:g.1001461T>C`, `NM_000109.4:c.5700T>C`, `NM_004006.3:c.5724T>C`, `NM_004009.3:c.5712T>C`, `NM_004010.3:c.5355T>C`, `NM_004011.4:c.1701T>C`, `NM_004012.4:c.1692T>C`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 5.06%, afr) — too common for a highly-penetrant pathogenic allele.

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 9.271, GERP 2.93, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 7.888**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **no splice effect predicted**. SpliceAI outputs four numbers per variant, not one: acceptor loss, donor loss, acceptor gain, donor gain (DS_AL / DS_DL / DS_AG / DS_DG). A loss score is an existing splice site weakened or destroyed; a gain score is a new site created or an existing one strengthened. The release publishes its own filter rule, which we read from the dataset rather than assume: an allele is reported only if the largest of its four deltas reaches 0.2. No allele at this position is in the release, so all four are under 0.2 for every alternate allele here. No figure is shown because none was read: the bound is deduced from that absence. It is a result, not a gap in our data, because the release scores every possible substitution across the transcripts it covers (Ensembl MANE v1.4) before it filters, so what survives for a gene is one continuous stretch. What is measured is that this position sits inside the stretch covered for DMD (7,339 scored positions, the nearest 2 bases away); what is taken from the release's own description, rather than measured, is that coverage inside that stretch is continuous. On that, SpliceAI did score it. *ClinGen's SVI treats the largest of the four as evidence against a splicing effect at or below 0.1, where it may support BP4, and as uninformative between 0.1 and 0.2. We cannot tell which applies here, so these SpliceAI data support neither BP4 nor PP3; that is a statement about this evidence alone, not about the variant's other evidence.*
- Population frequency (gnomAD v4.1): grpmax **5.06%** (afr) · FAF95 4.91% · FAF99 4.85% · 2,888/57,037 in the highest group · 3,482/1,208,713 alleles overall — common (popmax 5.06%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 5.06% | 20 |
| Admixed American | 0.57% | 175 |
| Remaining individuals (not grpmax-eligible) | 0.448% | 223 |
| Middle Eastern | 0.299% | 334 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.15% | 667 |
| South Asian | 0.0194% | 5,159 |
| European (non-Finnish) | 0.00715% | 13,977 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**DMD** population constraint: ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **progressive muscular dystrophy** — Definitive (XL)

## Protein context {#protein}

Residue **1908** lies in the 'interaction with synm' region.

**6 experimental structure(s)** (PDB): [1DXX](https://www.rcsb.org/structure/1DXX), [1EG3](https://www.rcsb.org/structure/1EG3), [1EG4](https://www.rcsb.org/structure/1EG4), [3UUN](https://www.rcsb.org/structure/3UUN), [9D58](https://www.rcsb.org/structure/9D58), [9EC1](https://www.rcsb.org/structure/9EC1).

## What this gene does {#gene-function}

*Describes the biological roles of DMD (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** DMD's established molecular role includes dystroglycan binding. p.Asp1908= falls in the interaction with synm region.


### Pathways affected {#pathways}

DMD participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Striated Muscle Contraction](https://reactome.org/content/detail/R-HSA-390522) | curated |
| [Formation of the dystrophin-glycoprotein complex (DGC)](https://reactome.org/content/detail/R-HSA-9913351) | electronic |
| [Non-integrin membrane-ECM interactions](https://reactome.org/content/detail/R-HSA-3000171) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** dystroglycan binding, actin binding, structural constituent of muscle, myosin binding, vinculin binding.

**Biological process:** regulation of heart rate, intracellular protein localization, positive regulation of neuron projection development, peptide biosynthetic process, positive regulation of neuron differentiation, cardiac muscle contraction.

## Clinical significance {#significance}

**Benign/Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-03.

**Submitter consensus:** conflicting (14 Benign, 2 Likely benign).

**Submission history:** 16 submissions (2013–2026); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Athena Diagnostics | Benign | criteria provided, single submitter | clinical testing | 2017-09-19 |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Benign | criteria provided, single submitter | clinical testing | 2015-01-13 |
| Eurofins Ntd Llc (ga) | Benign | criteria provided, single submitter | clinical testing | 2013-09-13 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-03 |
| GeneDx | Benign | criteria provided, single submitter | clinical testing | 2014-08-06 |
| Illumina Laboratory Services, Illumina | Benign | criteria provided, single submitter | clinical testing | 2018-01-12 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Benign | criteria provided, single submitter | clinical testing | 2020-04-24 |
| Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | Benign | no assertion criteria provided | clinical testing |  |
| Genome Diagnostics Laboratory, University Medical Center Utrecht | Benign | no assertion criteria provided | clinical testing |  |
| Natera, Inc. | Likely benign | no assertion criteria provided | clinical testing | 2017-04-20 |
| Fulgent Genetics, Fulgent Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2021-09-01 |
| Ambry Genetics | Benign | criteria provided, single submitter | clinical testing | 2015-07-27 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Benign | criteria provided, single submitter | clinical testing | 2025-04-09 |
| Mayo Clinic Laboratories, Mayo Clinic | Benign | criteria provided, single submitter | clinical testing | 2022-04-26 |
| ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Benign | criteria provided, single submitter | clinical testing | 2025-05-14 |

## Associated conditions {#conditions}

[Becker muscular dystrophy](https://sugi.bio/atlas/disease/becker-muscular-dystrophy/), [cardiomyopathy](https://sugi.bio/atlas/disease/cardiomyopathy/), [dilated cardiomyopathy 3B](https://sugi.bio/atlas/disease/dilated-cardiomyopathy-3b/), [Duchenne muscular dystrophy](https://sugi.bio/atlas/disease/duchenne-muscular-dystrophy/).

**Reported phenotype names (ClinVar):** Becker muscular dystrophy, not specified, Dilated cardiomyopathy 3B, Cardiovascular phenotype, not provided, Duchenne muscular dystrophy, Cardiomyopathy, Dystrophin deficiency, Becker Muscular Dystrophy (BMD), MUSCULAR DYSTROPHY, PSEUDOHYPERTROPHIC PROGRESSIVE, BECKER TYPE.

## Similar variants {#similar}

Related DMD variant pages (same residue, condition, or type): [DMD p.Asp1908Val](/variant/dmd-p-asp1908val), [DMD c.10086+1G>A](/variant/dmd-c-10086-plus-1g-a), [DMD c.10086+1G>T](/variant/dmd-c-10086-plus-1g-t), [DMD c.10086+2T>C](/variant/dmd-c-10086-plus-2t-c), [DMD c.10087-2A>G](/variant/dmd-c-10087-minus-2a-g), [DMD c.10223+1G>A](/variant/dmd-c-10223-plus-1g-a), [DMD c.10223+1G>C](/variant/dmd-c-10223-plus-1g-c), [DMD c.10224-2A>G](/variant/dmd-c-10224-minus-2a-g).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 94679). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*