Is DMD p.Arg1350Cys (c.4048C>T) pathogenic?

DMD p.Arg1350Cys (c.4048C>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-07). AlphaMissense: likely benign (0.1694); Very rare (popmax 0.00592%, eas); Associated with dilated cardiomyopathy 3B.

What condition is associated with DMD p.Arg1350Cys (c.4048C>T)?

DMD p.Arg1350Cys (c.4048C>T) is associated with dilated cardiomyopathy 3B, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg1350Cys (c.4048C>T) in the general population?

DMD p.Arg1350Cys (c.4048C>T) is very rare (popmax 0.00592%, eas) (gnomAD).

What do computational predictors say about DMD p.Arg1350Cys (c.4048C>T)?

AlphaMissense predicts likely benign (score 0.1694) — an in-silico prediction, not a clinical call.

DMD p.Arg1350Cys

c.4048C>T · rs1278483491 · VCV1030735

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, eas)

Conditions

dilated cardiomyopathy 3B

Computational evidence

Protein change
AlphaMissense	0.1694	likely benign
REVEL	0.421	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	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	29.3	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 0.00592% East Asian · 2/33,784 alleles

Filtering AF 0.00098% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.001% 11/1,097,805 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00592%	16,892
South Asian	0.00176%	56,944
European (non-Finnish)	0.000894%	111,894

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.Arg1350Cys
Coding: c.4048C>T
MANE Select: NM_004006
dbSNP: rs1278483491
Type: single nucleotide variant
Location: chrX:32438264 (GRCh38)

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

Disease context

dilated cardiomyopathy 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Arg1350His Conflicting classifications of pathogenicity ★ ⚠ 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-arg1350cys (accessed [today's date]).

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