# NM_178151.2(DCX):c.367del

https://sugi.bio/variant/dcx-c-367del

## Summary

**DCX c.367del** is classified **Pathogenic** in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). No gnomAD frequency available for this variant; Associated with Ectopic tissue.

**At a glance:** Pathogenic · review: Single submitter · rsID rs587783545 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the DCX gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to Ectopic tissue.

*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 | [DCX](https://sugi.bio/atlas/gene/DCX/) |
| Coding change (HGVS c.) | c.367del |
| MANE Select transcript | [NM_001195553](https://www.ncbi.nlm.nih.gov/nuccore/NM_001195553) (variant reported on NM_178151) |
| dbSNP | [rs587783545](https://www.ncbi.nlm.nih.gov/snp/rs587783545/) |
| Variant type | Deletion |
| Location | chrX:111401328-111401328 (GRCh38) |
| ClinVar | [VCV158457](https://www.ncbi.nlm.nih.gov/clinvar/variation/158457/) |

**All HGVS expressions:** `NC_000023.10:g.110644559del`, `NC_000023.11:g.111401331del`, `NG_011750.1:g.15851del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 6.214, GERP 2.09, phastCons 1 — highly conserved position (PP3-type support)
- 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: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**DCX** population constraint: ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *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):

- **lissencephaly spectrum disorders** — Definitive (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 67.19, 10% of residues very-high.

**14 experimental structure(s)** (PDB): [1MJD](https://www.rcsb.org/structure/1MJD), [2BQQ](https://www.rcsb.org/structure/2BQQ), [2XRP](https://www.rcsb.org/structure/2XRP), [4ATU](https://www.rcsb.org/structure/4ATU), [5IKC](https://www.rcsb.org/structure/5IKC), [5IN7](https://www.rcsb.org/structure/5IN7).

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

*Describes the biological roles of DCX (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:** DCX's established molecular role includes microtubule binding.


### Pathways affected {#pathways}

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

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Neurofascin interactions](https://reactome.org/content/detail/R-HSA-447043) | electronic |

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

**Molecular function:** microtubule binding, protein kinase binding.

**Biological process:** neuron migration.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2013-02-08.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Genetic Services Laboratory, University of Chicago | Pathogenic | criteria provided, single submitter | clinical testing | 2013-02-08 |

## Associated conditions {#conditions}

[Ectopic tissue](https://sugi.bio/atlas/disease/ectopic-tissue/).

**Reported phenotype names (ClinVar):** Ectopic tissue, Heterotopia.

## Similar variants {#similar}

Related DCX variant pages (same residue, condition, or type): [DCX p.Asn131del](/variant/dcx-p-asn131del), [DCX p.Ile218fs](/variant/dcx-p-ile218fs), [DCX p.Lys193fs](/variant/dcx-p-lys193fs), [DCX p.Lys51fs](/variant/dcx-p-lys51fs), [DCX p.Ser165fs](/variant/dcx-p-ser165fs), [DCX p.Thr42fs](/variant/dcx-p-thr42fs), [DCX p.Val224fs](/variant/dcx-p-val224fs), [DCX p.Ala204Asp](/variant/dcx-p-ala204asp).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 158457). 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.*