# NM_001939.3(DRP2):c.981A>G (p.Ser327=)

https://sugi.bio/variant/drp2-p-ser327

## Summary

**DRP2 p.Ser327= (c.981A>G)** is classified **Benign** in DRP2 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-10-28). Rare (popmax 0.92%, eas).

**At a glance:** Benign · review: Single submitter · rsID rs78348084 · 3 submitters · rare (popmax 0.92%, eas)

## For patients & families {#patients}

This is a change in the DRP2 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 | [DRP2](https://sugi.bio/atlas/gene/DRP2/) |
| Protein change (HGVS p.) | p.Ser327= |
| Coding change (HGVS c.) | c.981A>G |
| MANE Select transcript | [NM_001197293](https://www.ncbi.nlm.nih.gov/nuccore/NM_001197293) (variant reported on NM_001939) |
| dbSNP | [rs78348084](https://www.ncbi.nlm.nih.gov/snp/rs78348084/) |
| Variant type | single nucleotide variant |
| Location | chrX:101242909-101242909 (GRCh38) |
| ClinVar | [VCV1624598](https://www.ncbi.nlm.nih.gov/clinvar/variation/1624598/) |

**All HGVS expressions:** `NC_000023.10:g.100497898A>G`, `NC_000023.11:g.101242909A>G`, `NG_016403.1:g.27966A>G`, `NM_001171184.2:c.747A>G`, `NM_001939.2:c.981A>G`, `NM_001939.3:c.981A>G`

## 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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor gain** (Δ 0.20) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP 1.679, GERP -3.37, phastCons 1 — weakly conserved position
- CADD: **PHRED 6.674**. 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 deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.20**, donor gain **0.00**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.20**, donor gain **0.00**.
- Population frequency (gnomAD v4.1): grpmax **0.92%** (eas) · FAF95 0.835% · FAF99 0.802% · 310/33,711 in the highest group · 351/1,208,325 alleles overall — rare (popmax 0.92%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| East Asian (grpmax) | 0.92% | 109 |
| Remaining individuals (not grpmax-eligible) | 0.0462% | 2,162 |
| South Asian | 0.0282% | 3,540 |
| Admixed American | 0.00219% | 45,650 |
| European (non-Finnish) | 0.000224% | 447,149 |

*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}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-10-28.

**Submitter consensus:** unanimous (2/2 Benign).

**Submission history:** 3 submissions (2019–2025); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Benign | no assertion criteria provided | clinical testing | 2019-06-18 |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2025-10-28 |

**Reported phenotype names (ClinVar):** not provided, DRP2-related disorder, Cervical cancer, none provided, DRP2-related condition.

## Similar variants {#similar}

Related DRP2 variant pages (same residue, condition, or type): [DRP2 p.Glu432Ter](/variant/drp2-p-glu432ter), [DPYSL2 p.Asn492Ser](/variant/dpysl2-p-asn492ser), [DPYSL2 p.Asp520Asn](/variant/dpysl2-p-asp520asn), [DRP2 p.Ala205Val](/variant/drp2-p-ala205val), [DRP2 p.Ala643Thr](/variant/drp2-p-ala643thr), [DRP2 p.Arg199His](/variant/drp2-p-arg199his), [DRP2 p.Arg224Cys](/variant/drp2-p-arg224cys), [DRP2 p.Arg224His](/variant/drp2-p-arg224his).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 1624598). 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.*