Is DCX p.Arg272Ter (c.814C>T) pathogenic?

DCX p.Arg272Ter (c.814C>T) is classified Pathogenic in DCX (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-01-10). Very rare (popmax 9.11e-05%); Associated with lissencephaly type 1 due to doublecortin gene mutation.

What condition is associated with DCX p.Arg272Ter (c.814C>T)?

DCX p.Arg272Ter (c.814C>T) is associated with lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Arg272Ter (c.814C>T) in the general population?

DCX p.Arg272Ter (c.814C>T) is very rare (popmax 9.11e-05%) (gnomAD).

DCX p.Arg272Ter

Q: How is Lissencephaly type 1 due to doublecortin gene mutation inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.814C>T · rs587783590 · VCV158509

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Conditions

lissencephaly type 1 due to doublecortin gene mutation

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 5 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.73, phastCons 1
Overall
CADD	36.0	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 9.11e-05%

Overall 9.11e-05% 1/1,097,264 alleles · very rare

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.Arg272Ter
Coding: c.814C>T
MANE Select: NM_001195553
dbSNP: rs587783590
Type: single nucleotide variant
Location: chrX:111331036 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB

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

Disease context

lissencephaly type 1 due to doublecortin gene mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lissencephaly type 1 due to doublecortin gene mutation (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

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.Arg303Ter Pathogenic ★★ same condition
DCX p.Arg39Ter 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-arg272ter (accessed [today's date]).

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