# NM_001939.3(DRP2):c.86del (p.Ser29fs)

https://sugi.bio/variant/drp2-p-ser29fs

## Summary

**DRP2 p.Ser29fs (c.86del)** is classified **Uncertain significance** in DRP2 (ClinVar, No assertion criteria, 2 submitters). Very rare (popmax 0.000447%, nfe).

**At a glance:** Uncertain significance · review: No assertion criteria · rsID rs2147332623 · 2 submitters · very rare (popmax 0.000447%, nfe)

## For patients & families {#patients}

This is a change in the DRP2 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 2 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 | [DRP2](https://sugi.bio/atlas/gene/DRP2/) |
| Protein change (HGVS p.) | p.Ser29fs |
| Coding change (HGVS c.) | c.86del |
| MANE Select transcript | [NM_001197293](https://www.ncbi.nlm.nih.gov/nuccore/NM_001197293) (variant reported on NM_001939) |
| dbSNP | [rs2147332623](https://www.ncbi.nlm.nih.gov/snp/rs2147332623/) |
| Variant type | Deletion |
| Location | chrX:101231733-101231733 (GRCh38) |
| ClinVar | [VCV1297513](https://www.ncbi.nlm.nih.gov/clinvar/variation/1297513/) |

**All HGVS expressions:** `NC_000023.10:g.100486722del`, `NC_000023.11:g.101231733del`, `NG_016403.1:g.16790del`, `NM_001171184.2:c.-117-4127del`, `NM_001939.3:c.86del`

## 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 1.623, GERP 0.489, phastCons 0.947 — weakly conserved position
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- 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 **0.000447%** (nfe) · FAF95 0.000105% · FAF99 7.1e-05% · 4/895,163 in the highest group · 4/1,097,863 alleles overall — very rare (popmax 0.000447%, nfe).

*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.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 90.49, 82% of residues very-high.

**15 experimental structure(s)** (PDB): [2GSE](https://www.rcsb.org/structure/2GSE), [2VM8](https://www.rcsb.org/structure/2VM8), [5LXX](https://www.rcsb.org/structure/5LXX), [5MKV](https://www.rcsb.org/structure/5MKV), [5MLE](https://www.rcsb.org/structure/5MLE), [5X1A](https://www.rcsb.org/structure/5X1A) — incl. mutant structure 5MLE.

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

*Describes the biological roles of DRP2 (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:** DRP2's established molecular role includes identical protein binding.


### Pathways affected {#pathways}

DRP2 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [CRMPs in Sema3A signaling](https://reactome.org/content/detail/R-HSA-399956) | curated |
| [Recycling pathway of L1](https://reactome.org/content/detail/R-HSA-437239) | curated |

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

**Molecular function:** identical protein binding.

**Biological process:** endocytosis.

## Clinical significance {#significance}

**Uncertain significance** — review status No assertion criteria *(no assertion criteria provided)*.

**Submitter consensus:** unanimous (2/2 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | Uncertain significance | no assertion criteria provided | clinical testing |  |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Uncertain significance | no assertion criteria provided | clinical testing |  |

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

## Similar variants {#similar}

Related DRP2 variant pages (same residue, condition, or type): [DRP2 c.1677_1698+44del](/variant/drp2-c-1677-1698-plus-44del), [DRP2 p.Ala127fs](/variant/drp2-p-ala127fs), [DRP2 p.Glu838fs](/variant/drp2-p-glu838fs), [DRP2 p.Phe769fs](/variant/drp2-p-phe769fs), [DRP2 p.Pro174fs](/variant/drp2-p-pro174fs), [DRP2 p.Ser776fs](/variant/drp2-p-ser776fs), [DPYSL2 p.Ala405fs](/variant/dpysl2-p-ala405fs), [DPYSL2 p.Gly91fs](/variant/dpysl2-p-gly91fs).

### 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 1297513). 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.*