# NM_001389.5(DSCAM):c.2352T>G (p.Val784=)

https://sugi.bio/variant/dscam-p-val784

## Summary

**DSCAM p.Val784= (c.2352T>G)** is classified **Likely benign** in DSCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). Absent from gnomAD v4.1.

**At a glance:** Likely benign · review: Single submitter · rsID rs2073682831 · 1 submitter · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the DSCAM gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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 | [DSCAM](https://sugi.bio/atlas/gene/DSCAM/) |
| Protein change (HGVS p.) | p.Val784= |
| Coding change (HGVS c.) | c.2352T>G |
| MANE Select transcript | [NM_001389](https://www.ncbi.nlm.nih.gov/nuccore/NM_001389) |
| dbSNP | [rs2073682831](https://www.ncbi.nlm.nih.gov/snp/rs2073682831/) |
| Variant type | single nucleotide variant |
| Location | chr21:40276101-40276101 (GRCh38) |
| ClinVar | [VCV2498897](https://www.ncbi.nlm.nih.gov/clinvar/variation/2498897/) |

**All HGVS expressions:** `NC_000021.8:g.41648028A>C`, `NC_000021.9:g.40276101A>C`, `NM_001271534.3:c.2352T>G`, `NM_001389.5:c.2352T>G`, `NM_206887.1:c.2352T>G`, `NR_073202.3:n.2849T>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 (below), not from a missing predictor score.
- Conservation: phyloP -0.127, GERP -3.47, phastCons 0.077 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 4.91**. 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: **below the reporting threshold**. This position is scored for a different substitution (A>T, Δ0.42 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*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}

**DSCAM** population constraint: LOEUF 0.28, pLI 1, missense-Z 4.4469; ClinGen dosage — haploinsufficiency 2, 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.*

## Protein context {#protein}

Residue **784** lies in a β-strand.

AlphaFold model confidence (whole protein): pLDDT 69.98, 6% of residues very-high.

**1 experimental structure(s)** (PDB): [6ZR7](https://www.rcsb.org/structure/6ZR7).

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

*Describes the biological roles of DSCAM (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:** DSCAM's established molecular role includes netrin receptor binding.


### Pathways affected {#pathways}

DSCAM participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [DSCAM interactions](https://reactome.org/content/detail/R-HSA-376172) | electronic |

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

**Molecular function:** netrin receptor binding.

**Biological process:** positive regulation of phosphorylation, positive regulation of axon extension involved in axon guidance.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-11-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2023-11-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related DSCAM variant pages (same residue, condition, or type): [DSCAM p.Ser682Arg](/variant/dscam-p-ser682arg), [DSCAM c.5383+9T>A](/variant/dscam-c-5383-plus-9t-a), [DSCAM p.Ala153=](/variant/dscam-p-ala153), [DSCAM p.Arg1798=](/variant/dscam-p-arg1798), [DSCAM p.Asn1250=](/variant/dscam-p-asn1250), [DSCAM p.Asn576=](/variant/dscam-p-asn576), [DSCAM p.Asp185=](/variant/dscam-p-asp185), [DSCAM p.Gln582=](/variant/dscam-p-gln582).

### 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 2498897). 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.*