Is DCX p.Arg303Gln (c.908G>A) pathogenic?

DCX p.Arg303Gln (c.908G>A) is classified Conflicting classifications of pathogenicity in DCX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-06-07). AlphaMissense: ambiguous (0.4057); Ultra-rare (popmax 0.0148%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCX p.Arg303Gln (c.908G>A)?

DCX p.Arg303Gln (c.908G>A) is associated with Inborn genetic diseases, lissencephaly spectrum disorders (ClinVar).

How common is DCX p.Arg303Gln (c.908G>A) in the general population?

DCX p.Arg303Gln (c.908G>A) is ultra-rare (popmax 0.0148%, eas) (gnomAD).

What do computational predictors say about DCX p.Arg303Gln (c.908G>A)?

AlphaMissense predicts ambiguous (score 0.4057) — an in-silico prediction, not a clinical call.

DCX p.Arg303Gln

c.908G>A · rs753011298 · VCV2064870

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4057	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -8.47	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · 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

Grpmax group 0.0148% East Asian · 5/33,773 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00373%

Overall 0.0014% 17/1,210,546 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0148%	6,755
Remaining individualsnot grpmax-eligible	0.0021%	47,603
South Asian	0.00176%	56,856
European (non-Finnish)	0.00112%	89,536

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.Arg303Gln
Coding: c.908G>A
MANE Select: NM_001195553
dbSNP: rs753011298
Type: single nucleotide variant
Location: chrX:111330942 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 303: the 'disordered' region

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 spectrum disorders

Similar variants

DCX p.Arg303Ter Pathogenic ★★ same residue
DCX p.Arg196His Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg39Ter Pathogenic ★★ same condition
DCX p.Arg78Leu Pathogenic ★★ same condition
DCX p.Ala295Thr Uncertain significance ★★ ⚠ same condition
DCX p.Cys35Arg Uncertain significance ★★ ⚠ same condition
DCX p.Ile107Thr Uncertain significance ★★ ⚠ same condition
DCX c.706-4A>G Benign/Likely benign ★★ 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-arg303gln (accessed [today's date]).

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