Is DMD p.Arg2415Cys (c.7243C>T) pathogenic?

DMD p.Arg2415Cys (c.7243C>T) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.071); Rare (popmax 0.161%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg2415Cys (c.7243C>T)?

DMD p.Arg2415Cys (c.7243C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg2415Cys (c.7243C>T) in the general population?

DMD p.Arg2415Cys (c.7243C>T) is rare (popmax 0.161%, afr) (gnomAD).

What do computational predictors say about DMD p.Arg2415Cys (c.7243C>T)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

DMD p.Arg2415Cys

c.7243C>T · rs139395045 · VCV166702

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.125	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 3.9	GERP -0.58, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	17.77	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 0.161% African / African-American · 92/57,209 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0104% 126/1,209,890 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	622
Middle Eastern	0.023%	4,349
Remaining individualsnot grpmax-eligible	0.0147%	6,801
Admixed American	0.00874%	11,438
East Asian	0.00593%	16,871
South Asian	0.00352%	28,409
European (non-Finnish)	0.00201%	49,727

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.Arg2415Cys
Coding: c.7243C>T
MANE Select: NM_004006
dbSNP: rs139395045
Type: single nucleotide variant
Location: chrX:31820041 (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.Arg2415His Benign/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-arg2415cys (accessed [today's date]).

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