Is DMD p.Arg1350His (c.4049G>A) pathogenic?

DMD p.Arg1350His (c.4049G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-08-14). AlphaMissense: likely benign (0.096); Very rare (popmax 0.00438%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg1350His (c.4049G>A)?

DMD p.Arg1350His (c.4049G>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg1350His (c.4049G>A) in the general population?

DMD p.Arg1350His (c.4049G>A) is very rare (popmax 0.00438%, amr) (gnomAD).

What do computational predictors say about DMD p.Arg1350His (c.4049G>A)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

DMD p.Arg1350His

c.4049G>A · rs750981128 · VCV290184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00438%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.162	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.3	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 0.00438% Admixed American · 2/45,683 alleles

Filtering AF 0.00273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00339% 41/1,209,514 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00438%	22,841
Remaining individualsnot grpmax-eligible	0.0042%	23,793
European (non-Finnish)	0.0038%	26,322
South Asian	0.00352%	28,414
Finnishnot grpmax-eligible	0.00215%	46,542

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.Arg1350His
Coding: c.4049G>A
MANE Select: NM_004006
dbSNP: rs750981128
Type: single nucleotide variant
Location: chrX:32438263 (GRCh38)

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: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Arg1350Cys Uncertain significance ★★ same residue
DMD p.Arg1350Leu 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

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-arg1350his (accessed [today's date]).

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