Is DMD p.Arg3345Gln (c.10034G>A) pathogenic?

DMD p.Arg3345Gln (c.10034G>A) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-20). AlphaMissense: likely pathogenic (0.9606); Very rare (popmax 0.00175%, afr); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg3345Gln (c.10034G>A)?

DMD p.Arg3345Gln (c.10034G>A) is associated with Duchenne muscular dystrophy, dilated cardiomyopathy (ClinVar).

How common is DMD p.Arg3345Gln (c.10034G>A) in the general population?

DMD p.Arg3345Gln (c.10034G>A) is very rare (popmax 0.00175%, afr) (gnomAD).

How is Duchenne muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Arg3345Gln (c.10034G>A)?

AlphaMissense predicts likely pathogenic (score 0.9606) — an in-silico prediction, not a clinical call.

DMD p.Arg3345Gln

c.10034G>A · rs2041036250 · VCV1804758

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9606	likely pathogenic · top 8% in DMD
REVEL	0.83	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 3.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 170 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00175% African / African-American · 1/56,994 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000414% 5/1,208,699 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00175%	56,994
European (non-Finnish)	0.000447%	223,595

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.Arg3345Gln
Coding: c.10034G>A
MANE Select: NM_004006
dbSNP: rs2041036250
Type: single nucleotide variant
Location: chrX:31180422 (GRCh38)
Residue 3345: the 'interaction with synm' region

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

Disease context

Duchenne muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Arg3345Ter Pathogenic ★★ same residue
DMD p.Arg3345Gly Uncertain significance ★★ ⚠ same residue
DMD p.Arg3345Pro Uncertain significance ★★ ⚠ same residue
DMD p.Arg3345= Likely benign ★ same residue
DMD p.Arg3345fs Likely pathogenic ★ 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

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-arg3345gln (accessed [today's date]).

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