# NM_004006.3(DMD):c.960+50del

https://sugi.bio/variant/dmd-c-960-plus-50del

## Summary

**DMD c.960+50del** is classified **Benign** in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-06-14). Common (popmax 19.1%, afr) — too common for a highly-penetrant pathogenic allele.

**At a glance:** Benign · review: Multiple submitters · rsID rs72470512 · 3 submitters · common (popmax 19.1%, 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 — not considered disease-causing, submitted by 3 submitters.

*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.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DMD](https://sugi.bio/atlas/gene/DMD/) |
| Coding change (HGVS c.) | c.960+50del |
| MANE Select transcript | [NM_004006](https://www.ncbi.nlm.nih.gov/nuccore/NM_004006) |
| dbSNP | [rs72470512](https://www.ncbi.nlm.nih.gov/snp/rs72470512/) |
| Variant type | Deletion |
| Location | chrX:32697820-32697820 (GRCh38) |
| ClinVar | [VCV94848](https://www.ncbi.nlm.nih.gov/clinvar/variation/94848/) |

**All HGVS expressions:** `LRG_199:g.646790del`, `NC_000023.10:g.32715937del`, `NC_000023.11:g.32697820del`, `NG_012232.1:g.646790del`, `NM_000109.4:c.936+50del`, `NM_004006.2:c.960+50delG`, `NM_004006.3:c.960+50del`, `NM_004009.3:c.948+50del`, `NM_004010.3:c.591+50del`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 19.1%, 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 0.92, GERP 0.611, phastCons 0.001 — weakly conserved position
- CADD: **PHRED 0.145**. 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.*
- Splice region: **near-intronic (+50 nt from the splice site)**.
- Non-coding constraint (Gnocchi): **not assessed** — the gnomAD non-coding genomic-constraint release is computed on the autosomes only, so chrX has no window. That is a property of the dataset, not of the variant: it is not evidence that the region is unconstrained.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **19.1%** (afr) · FAF95 18.8% · FAF99 18.7% · 10,884/56,838 in the highest group · 12,631/1,202,413 alleles overall — common (popmax 19.1%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 19.1% | 5 |
| Remaining individuals (not grpmax-eligible) | 1.55% | 64 |
| Admixed American | 1.44% | 70 |
| Middle Eastern | 0.923% | 108 |
| South Asian | 0.0855% | 1,170 |
| European (non-Finnish) | 0.0302% | 3,307 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00913% | 10,954 |

*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, triplosensitivity 0 (0–3 scale). *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}


**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.


### 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** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2018-06-14.

**Submitter consensus:** unanimous (3/3 Benign).

**Submission history:** 3 submissions (2014–2020); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Eurofins Ntd Llc (ga) | Benign | criteria provided, single submitter | clinical testing | 2014-02-10 |
| GeneDx | Benign | criteria provided, single submitter | clinical testing | 2018-06-14 |
| Natera, Inc. | Benign | no assertion criteria provided | clinical testing | 2020-09-16 |

**Reported phenotype names (ClinVar):** not specified, not provided, Dystrophin deficiency, AllHighlyPenetrant, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related DMD variant pages (same residue, condition, or type): [DMD c.1813-29_1813-2del](/variant/dmd-c-1813-minus-29-1813-minus-2del), [DMD c.2804-1del](/variant/dmd-c-2804-minus-1del), [DMD c.3276+2del](/variant/dmd-c-3276-plus-2del), [DMD c.3433-5_3434del](/variant/dmd-c-3433-minus-5-3434del), [DMD c.4519-2_4523del](/variant/dmd-c-4519-minus-2-4523del), [DMD c.6438+1_6438+5del](/variant/dmd-c-6438-plus-1-6438-plus-5del), [DMD c.9650-4_9655del](/variant/dmd-c-9650-minus-4-9655del), [DMD p.Ala192fs](/variant/dmd-p-ala192fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 94848). 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.*