Is DMD p.Arg1735Cys (c.5203C>T) pathogenic?

DMD p.Arg1735Cys (c.5203C>T) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-03-15). AlphaMissense: likely benign (0.1236); Rare (popmax 0.155%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg1735Cys (c.5203C>T)?

DMD p.Arg1735Cys (c.5203C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg1735Cys (c.5203C>T) in the general population?

DMD p.Arg1735Cys (c.5203C>T) is rare (popmax 0.155%, afr) (gnomAD).

What do computational predictors say about DMD p.Arg1735Cys (c.5203C>T)?

AlphaMissense predicts likely benign (score 0.1236) — an in-silico prediction, not a clinical call.

DMD p.Arg1735Cys

c.5203C>T · rs147904018 · VCV201749

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1236 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.155%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1236	likely benign
REVEL	0.287	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 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	25.2	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 0.155% African / African-American · 88/56,876 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.119%

Overall 0.0103% 125/1,208,735 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.155%	646
Middle Eastern	0.0229%	4,372
Remaining individualsnot grpmax-eligible	0.0147%	6,795
South Asian	0.00704%	14,201
European (non-Finnish)	0.00268%	37,285
Admixed American	0.0022%	45,494

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.Arg1735Cys
Coding: c.5203C>T
MANE Select: NM_004006
dbSNP: rs147904018
Type: single nucleotide variant
Location: chrX:32362910 (GRCh38)
Residue 1735: the 'interaction with synm' region

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 dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

DMD p.Arg1735Ser Uncertain significance ★★ ⚠ same residue
DMD p.Arg1735His Conflicting classifications of pathogenicity ★ ⚠ 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-arg1735cys (accessed [today's date]).

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