Is DCX p.Ser47Arg (c.139A>C) pathogenic?

DCX p.Ser47Arg (c.139A>C) is classified Conflicting classifications of pathogenicity in DCX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-05-11). AlphaMissense: likely pathogenic (0.993); Absent from gnomAD v4.1; Associated with DCX-related disorder.

What condition is associated with DCX p.Ser47Arg (c.139A>C)?

DCX p.Ser47Arg (c.139A>C) is associated with DCX-related disorder, lissencephaly type 1 due to doublecortin gene mutation (ClinVar).

How common is DCX p.Ser47Arg (c.139A>C) in the general population?

DCX p.Ser47Arg (c.139A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Ser47Arg (c.139A>C)?

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

DCX p.Ser47Arg

c.139A>C · rs104894783 · VCV11603

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DCX-related disorder

Computational evidence

Protein change
AlphaMissense	0.993	likely pathogenic
REVEL	0.766	pathogenic-leaning
SaProt	LLR -12.62	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 7.9	GERP 0.87, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCX
Protein: p.Ser47Arg
Coding: c.139A>C
MANE Select: NM_001195553
dbSNP: rs104894783
Type: single nucleotide variant
Location: chrX:111410260 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 47: a UniProt-annotated variant site (in lisx1 and sbhx); a modified residue (phosphoserine; by mark1 and pka)

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

Disease context

Also linked: lissencephaly type 1 due to doublecortin gene mutation

Similar variants

DCX c.364+1G>A Likely pathogenic ★★ 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
DCX p.Arg19Ter 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-ser47arg (accessed [today's date]).

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