Is DCX p.Asp349His (c.1045G>C) pathogenic?

DCX p.Asp349His (c.1045G>C) is classified Uncertain significance in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2015-11-12). AlphaMissense: likely pathogenic (0.7629); Absent from gnomAD v4.1.

How common is DCX p.Asp349His (c.1045G>C) in the general population?

DCX p.Asp349His (c.1045G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Asp349His (c.1045G>C)?

AlphaMissense predicts likely pathogenic (score 0.7629) — an in-silico prediction, not a clinical call.

DCX p.Asp349His

c.1045G>C · rs1556364322 · VCV434899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7629 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7629	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.37	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D348H vs ClinVar D349H) — verify the residue.

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.Asp349His
Coding: c.1045G>C
MANE Select: NM_001195553
dbSNP: rs1556364322
Type: single nucleotide variant
Location: chrX:111301743 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 349: the 'disordered' region

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-asp349his (accessed [today's date]).

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