Is DCX p.Arg102His (c.305G>A) pathogenic?

DCX p.Arg102His (c.305G>A) is classified Conflicting classifications of pathogenicity in DCX (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2019-10-15). AlphaMissense: likely pathogenic (0.993); Absent from gnomAD v4.1; Associated with lissencephaly type 1 due to doublecortin gene mutation.

What condition is associated with DCX p.Arg102His (c.305G>A)?

DCX p.Arg102His (c.305G>A) is associated with lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Arg102His (c.305G>A) in the general population?

DCX p.Arg102His (c.305G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Arg102His (c.305G>A)?

AlphaMissense predicts likely pathogenic (score 0.993) — an in-silico prediction, not a clinical call.

DCX p.Arg102His

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.305G>A · rs267606317 · VCV82052

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.993 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,209,999)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lissencephaly type 1 due to doublecortin gene mutation

Computational evidence

Protein change
AlphaMissense	0.993	likely pathogenic
REVEL	0.946	strongly pathogenic-leaning
SaProt	LLR -10.99	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	27.1	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

No allele count reported in gnomAD v4.1 (AN 1,209,999). 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.Arg102His
Coding: c.305G>A
MANE Select: NM_001195553
dbSNP: rs267606317
Type: single nucleotide variant
Location: chrX:111410094 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 102: the doublecortin 1 domain; a UniProt-annotated variant site (in lisx1)

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.Arg102Ser Pathogenic ★ same residue
DCX p.Arg102Gly Pathogenic ★ same residue
DCX p.Arg102Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DCX p.Arg102= Likely benign ★ same residue
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

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-arg102his (accessed [today's date]).

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