Is DCX p.Asp130Gly (c.389A>G) pathogenic?

DCX p.Asp130Gly (c.389A>G) is classified Uncertain significance in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-28). AlphaMissense: likely pathogenic (0.6643); Very rare (popmax 0.000112%, nfe).

How common is DCX p.Asp130Gly (c.389A>G) in the general population?

DCX p.Asp130Gly (c.389A>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about DCX p.Asp130Gly (c.389A>G)?

AlphaMissense predicts likely pathogenic (score 0.6643) — an in-silico prediction, not a clinical call.

DCX p.Asp130Gly

c.389A>G · rs1064795427 · VCV421889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6643	likely pathogenic
REVEL	0.308	indeterminate
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP -2, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	22.7	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 0.000112% European (non-Finnish) · 1/895,168 alleles

Overall 9.11e-05% 1/1,097,682 alleles · very rare

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.Asp130Gly
Coding: c.389A>G
MANE Select: NM_001195553
dbSNP: rs1064795427
Type: single nucleotide variant
Location: chrX:111401306 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 130: the doublecortin 1 domain; a β-strand

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

Similar variants

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
DCX p.Ala251Ser Pathogenic ★★ same type
DCX p.Arg178Cys Pathogenic/Likely pathogenic ★★ same type
DCX p.Arg186Cys 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-asp130gly (accessed [today's date]).

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