Is DCX p.Arg196= (c.588T>C) pathogenic?

DCX p.Arg196= (c.588T>C) is classified Benign/Likely benign in DCX (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-20). Low-frequency (popmax 1.21%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCX p.Arg196= (c.588T>C)?

DCX p.Arg196= (c.588T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCX p.Arg196= (c.588T>C) in the general population?

DCX p.Arg196= (c.588T>C) is low-frequency (popmax 1.21%, afr) (gnomAD).

DCX p.Arg196=

c.588T>C · rs138706968 · VCV158486

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.088	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -4.2, phastCons 0.001
Overall
CADD	5.582	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.21% African / African-American · 693/57,135 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.0661% 800/1,209,805 alleles · low-frequency exomes 414/1,098,117 · genomes 386/111,688 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	82
Remaining individualsnot grpmax-eligible	0.118%	850
Admixed American	0.101%	993
South Asian	0.00352%	28,387
European (non-Finnish)	0.000335%	298,409

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DCX
Protein: p.Arg196=
Coding: c.588T>C
MANE Select: NM_001195553
dbSNP: rs138706968
Type: single nucleotide variant
Location: chrX:111401107 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same residue
DCX p.Arg196Cys Pathogenic ★★ same residue
DCX p.Arg196Gly Pathogenic ★ same residue
DCX p.Arg196Leu Uncertain significance ★ ⚠ same residue
DCX p.Arg196Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DCX p.Arg39Ter Pathogenic ★★ same condition
DCX p.Ala295Thr Uncertain significance ★★ ⚠ same condition
DCX p.Cys35Arg Uncertain significance ★★ ⚠ 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-arg196 (accessed [today's date]).

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