Is DCX p.Arg196Cys (c.586C>T) pathogenic?

DCX p.Arg196Cys (c.586C>T) is classified Pathogenic in DCX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-08). AlphaMissense: likely pathogenic (0.9976); Absent from gnomAD v4.1; Associated with Ectopic tissue.

What condition is associated with DCX p.Arg196Cys (c.586C>T)?

DCX p.Arg196Cys (c.586C>T) is associated with Ectopic tissue, lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Arg196Cys (c.586C>T) in the general population?

DCX p.Arg196Cys (c.586C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Arg196Cys (c.586C>T)?

AlphaMissense predicts likely pathogenic (score 0.9976) — an in-silico prediction, not a clinical call.

DCX p.Arg196Cys

c.586C>T · rs587783568 · VCV158485

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9976 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,211,412)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ectopic tissue

Computational evidence

Protein change
AlphaMissense	0.9976	likely pathogenic ✓ concordant with ClinVar
REVEL	0.931	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.28, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,211,412). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DCX
Protein: p.Arg196Cys
Coding: c.586C>T
MANE Select: NM_001195553
dbSNP: rs587783568
Type: single nucleotide variant
Location: chrX:111401109 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 196: the doublecortin 2 domain; a UniProt-annotated variant site (in lisx1); a UniProt-annotated variant site (in epilepsy; resistant partial seizures; related to 'cryptogenic' epilepsy); a β-strand

Full DCX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ectopic tissue — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lissencephaly type 1 due to doublecortin gene mutation

Similar variants

DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same residue
DCX p.Arg196Gly Pathogenic ★ same residue
DCX p.Arg196Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DCX p.Arg196= Benign/Likely benign ★★ same residue
DCX p.Arg196Leu Uncertain significance ★ ⚠ same residue
DCX c.809-1G>A Pathogenic/Likely pathogenic ★★ same condition
DCX p.Ala204Asp Pathogenic ★★ same condition
DCX p.Ala251Ser Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dcx-p-arg196cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown