Is DCX p.Arg196Ser (c.586C>A) pathogenic?

DCX p.Arg196Ser (c.586C>A) is classified Conflicting classifications of pathogenicity in DCX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-04-18). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Ectopic tissue.

What condition is associated with DCX p.Arg196Ser (c.586C>A)?

DCX p.Arg196Ser (c.586C>A) is associated with Ectopic tissue (ClinVar).

How common is DCX p.Arg196Ser (c.586C>A) in the general population?

DCX p.Arg196Ser (c.586C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Arg196Ser (c.586C>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

DCX p.Arg196Ser

c.586C>A · rs587783568 · VCV158483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ectopic tissue

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 6% in DCX
REVEL	0.854	moderately pathogenic-leaning
SaProt	LLR -13.65	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	27.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCX
Protein: p.Arg196Ser
Coding: c.586C>A
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

Similar variants

DCX p.Arg196Cys Pathogenic ★★ same residue
DCX p.Arg196Gly Pathogenic ★ same residue
DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same residue
DCX p.Arg196= Benign/Likely benign ★★ same residue
DCX p.Arg196Leu Uncertain significance ★ ⚠ same residue
DCX p.Ala204Asp Pathogenic ★★ same condition
DCX p.Ala251Ser Pathogenic ★★ same condition
DCX p.Arg186Cys 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-arg196ser (accessed [today's date]).

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