# NM_153741.2(DPM3):c.39C>T (p.Ile13=)

https://sugi.bio/variant/dpm3-p-ile13

## Summary

**DPM3 p.Ile13= (c.39C>T)** is classified **Likely benign** in DPM3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-03). Ultra-rare (popmax 0.0121%, sas); Associated with DPM3-congenital disorder of glycosylation.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs758221729 · 2 submitters · 1 linked condition · ultra-rare (popmax 0.0121%, sas)

## For patients & families {#patients}

This is a change in the DPM3 gene that is classified as likely benign — not considered disease-causing, submitted by 2 submitters, and is linked to DPM3-congenital disorder of glycosylation.

*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) | Autosomal recessive |
| Age of onset (of this condition) | Childhood |
| Diagnostic panels | DPM3 is a diagnostic-grade gene on 8 Genomics England panels |

**Commonly reported features of DPM3-CDG** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Decreased sialylation of O-linked protein glycosylation — Very frequent (99-80%)
- Reduced tendon reflexes — Frequent (79-30%)
- Muscle weakness — Frequent (79-30%)
- Dilated cardiomyopathy — Frequent (79-30%)
- Pes planus — Frequent (79-30%)
- Intellectual disability, profound — Frequent (79-30%)
- Stroke-like episode — Frequent (79-30%)
- Elevated circulating hepatic transaminase concentration — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0012395/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DPM3](https://sugi.bio/atlas/gene/DPM3/) |
| Protein change (HGVS p.) | p.Ile13= |
| Coding change (HGVS c.) | c.39C>T |
| MANE Select transcript | [NM_153741](https://www.ncbi.nlm.nih.gov/nuccore/NM_153741) |
| dbSNP | [rs758221729](https://www.ncbi.nlm.nih.gov/snp/rs758221729/) |
| Variant type | single nucleotide variant |
| Location | chr1:155140202-155140202 (GRCh38) |
| ClinVar | [VCV2738555](https://www.ncbi.nlm.nih.gov/clinvar/variation/2738555/) |

**All HGVS expressions:** `NC_000001.10:g.155112678G>A`, `NC_000001.11:g.155140202G>A`, `NG_012871.1:g.5319C>T`, `NM_018973.4:c.129C>T`, `NM_153741.2:c.39C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **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 0.182, GERP -1.67, phastCons 0.864 — weakly conserved position
- CADD: **PHRED 10.26**. 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: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.0121%** (sas) · FAF95 0.00676% · FAF99 0.00522% · 11/91,082 in the highest group · 40/1,614,166 alleles overall — ultra-rare (popmax 0.0121%, sas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| South Asian (grpmax) | 0.0121% | 8,280 |
| Remaining individuals (not grpmax-eligible) | 0.0064% | 15,628 |
| European (non-Finnish) | 0.00212% | 47,202 |

*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}

**DPM3** population constraint: LOEUF 1.364, pLI 0.0094613, missense-Z 0.50157; ClinGen dosage — haploinsufficiency 30, 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):

- **DPM3-congenital disorder of glycosylation** — Moderate (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.73, 64% of residues very-high.

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

*Describes the biological roles of DPM3 (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:** DPM3's established molecular role includes enzyme activator activity. In Reactome, DPM3 is annotated in disease pathway(s) including **Defective DPM1 causes DPM1-CDG**, **Defective DPM2 causes DPM2-CDG**.

**Disease mechanism (Reactome):** DPM3 loss or alteration is curated in [Defective DPM1 causes DPM1-CDG](https://reactome.org/content/detail/R-HSA-4717374), [Defective DPM2 causes DPM2-CDG](https://reactome.org/content/detail/R-HSA-4719377), [Defective DPM3 causes DPM3-CDG](https://reactome.org/content/detail/R-HSA-4719360).

### Pathways affected {#pathways}

DPM3 participates in **5 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective DPM1 causes DPM1-CDG](https://reactome.org/content/detail/R-HSA-4717374) | curated |
| ⚕ [Defective DPM2 causes DPM2-CDG](https://reactome.org/content/detail/R-HSA-4719377) | curated |
| ⚕ [Defective DPM3 causes DPM3-CDG](https://reactome.org/content/detail/R-HSA-4719360) | curated |
| ⚕ [Maturation of DENV proteins](https://reactome.org/content/detail/R-HSA-9918432) | curated |
| [Synthesis of dolichyl-phosphate mannose](https://reactome.org/content/detail/R-HSA-162699) | curated |

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

**Molecular function:** enzyme activator activity.

**Biological process:** dolichyl monophosphate biosynthetic process, dolichol phosphate mannose biosynthetic process.

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2023-04-03.

**Submitter consensus:** unanimous (2/2 Likely benign).

**Submission history:** 2 submissions (2021–2023); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2023-04-03 |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2021-09-07 |

## Associated conditions {#conditions}

[DPM3-congenital disorder of glycosylation](https://sugi.bio/atlas/disease/dpm3-congenital-disorder-of-glycosylation/).

**Reported phenotype names (ClinVar):** DPM3-congenital disorder of glycosylation, not specified, DPM3-CDG, MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 15, CDG Io, CDG1(DPM3), AllHighlyPenetrant.

## Similar variants {#similar}

Related DPM3 variant pages (same residue, condition, or type): [DPM3 p.Ala70Thr](/variant/dpm3-p-ala70thr), [DPM3 p.Ala86Asp](/variant/dpm3-p-ala86asp), [DPM3 p.Arg60Cys](/variant/dpm3-p-arg60cys), [DPM3 p.Arg60Leu](/variant/dpm3-p-arg60leu), [DPM3 p.Glu73Ala](/variant/dpm3-p-glu73ala), [DPM3 p.Gly89Glu](/variant/dpm3-p-gly89glu), [DPM3 p.Trp7Arg](/variant/dpm3-p-trp7arg), [DPM3 p.Tyr59Ser](/variant/dpm3-p-tyr59ser).

### 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 2738555). 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.*