Is DCX p.Tyr229fs (c.684_685del) pathogenic?

DCX p.Tyr229fs (c.684685del) is classified Pathogenic in DCX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2021-02-12). Absent from gnomAD; Associated with lissencephaly type 1 due to doublecortin gene mutation.

What condition is associated with DCX p.Tyr229fs (c.684_685del)?

DCX p.Tyr229fs (c.684_685del) is associated with lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Tyr229fs (c.684_685del) in the general population?

DCX p.Tyr229fs (c.684_685del) is absent from gnomAD (gnomAD).

DCX p.Tyr229fs

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.684_685del · rs1556401744 · VCV434900

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Tyr229fs
Coding: c.684_685del
MANE Select: NM_001195553
dbSNP: rs1556401744
Type: Microsatellite
Location: chrX:111401010 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 229: the doublecortin 2 domain; a β-strand

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 p.Tyr229_Gly233dup Pathogenic ★ same residue
DCX p.Lys202del Uncertain significance ★ same condition
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

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-tyr229fs (accessed [today's date]).

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