Is DCX p.Arg344Gln (c.1031G>A) pathogenic?

DCX p.Arg344Gln (c.1031G>A) is classified Uncertain significance in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-17). AlphaMissense: likely benign (0.1259); Very rare (popmax 0.00592%, eas); Associated with intellectual disability.

What condition is associated with DCX p.Arg344Gln (c.1031G>A)?

DCX p.Arg344Gln (c.1031G>A) is associated with intellectual disability (ClinVar).

How common is DCX p.Arg344Gln (c.1031G>A) in the general population?

DCX p.Arg344Gln (c.1031G>A) is very rare (popmax 0.00592%, eas) (gnomAD).

What do computational predictors say about DCX p.Arg344Gln (c.1031G>A)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

DCX p.Arg344Gln

c.1031G>A · VCV4072121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00592% East Asian · 2/33,758 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00372% 45/1,209,585 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00592%	16,879
European (non-Finnish)	0.00469%	21,311
Admixed American	0.00219%	45,729

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.Arg344Gln
Coding: c.1031G>A
MANE Select: NM_001195553
Type: single nucleotide variant
Location: chrX:111312652 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 344: the 'disordered' region

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCX p.Arg344Pro Uncertain significance ★ ⚠ same residue
DCX p.Arg344Trp Uncertain significance ★ ⚠ same residue
DCX p.Val197Met Uncertain significance ★ ⚠ same condition
DCX c.364+1G>A Likely pathogenic ★★ same type
DCX c.705+1G>A Pathogenic ★★ same type
DCX c.706-2A>G Pathogenic ★★ same type
DCX c.809-1G>A Pathogenic/Likely pathogenic ★★ same type
DCX p.Ala204Asp Pathogenic ★★ same type

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-arg344gln (accessed [today's date]).

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