Is DCX p.Arg39Ter (c.115C>T) pathogenic?

DCX p.Arg39Ter (c.115C>T) is classified Pathogenic in DCX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCX p.Arg39Ter (c.115C>T)?

DCX p.Arg39Ter (c.115C>T) is associated with Inborn genetic diseases, lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Arg39Ter (c.115C>T) in the general population?

DCX p.Arg39Ter (c.115C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

DCX p.Arg39Ter

c.115C>T · rs587783519 · VCV158425

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -2, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,471 alleles

Overall 8.25e-05% 1/1,211,491 alleles · very rare exomes 1/1,098,189 · genomes 0/113,302 · joint denominator

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.Arg39Ter
Coding: c.115C>T
MANE Select: NM_001195553
dbSNP: rs587783519
Type: single nucleotide variant
Location: chrX:111410284 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB

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

Also linked: lissencephaly type 1 due to doublecortin gene mutation

Similar variants

DCX c.809-1G>A Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg178Cys Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg186Leu Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg192Trp Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg196Cys Pathogenic ★★ same condition
DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg272Ter Pathogenic ★★ same condition
DCX p.Arg303Ter 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-arg39ter (accessed [today's date]).

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