Is DMD p.Glu349Asp (c.1047A>T) pathogenic?

DMD p.Glu349Asp (c.1047A>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-05). AlphaMissense: likely pathogenic (0.886); Very rare (popmax 0.000112%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Glu349Asp (c.1047A>T)?

DMD p.Glu349Asp (c.1047A>T) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Glu349Asp (c.1047A>T) in the general population?

DMD p.Glu349Asp (c.1047A>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about DMD p.Glu349Asp (c.1047A>T)?

AlphaMissense predicts likely pathogenic (score 0.886) — an in-silico prediction, not a clinical call.

DMD p.Glu349Asp

c.1047A>T · rs1044325754 · VCV447249

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.886	likely pathogenic
REVEL	0.266	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -2.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	19.38	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) · 1/895,468 alleles

Overall 9.11e-05% 1/1,098,091 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: DMD
Protein: p.Glu349Asp
Coding: c.1047A>T
MANE Select: NM_004006
dbSNP: rs1044325754
Type: single nucleotide variant
Location: chrX:32645066 (GRCh38)
Residue 349: an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Glu349= Likely benign ★ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G Likely 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/dmd-p-glu349asp (accessed [today's date]).

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