Is DMD p.Arg2263Cys (c.6787C>T) pathogenic?

DMD p.Arg2263Cys (c.6787C>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-30). AlphaMissense: likely benign (0.2589); Very rare (popmax 0.00593%, eas); Associated with Becker muscular dystrophy.

What condition is associated with DMD p.Arg2263Cys (c.6787C>T)?

DMD p.Arg2263Cys (c.6787C>T) is associated with Becker muscular dystrophy, cardiomyopathy, dilated cardiomyopathy 3B (ClinVar).

How common is DMD p.Arg2263Cys (c.6787C>T) in the general population?

DMD p.Arg2263Cys (c.6787C>T) is very rare (popmax 0.00593%, eas) (gnomAD).

How is Becker 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.Arg2263Cys (c.6787C>T)?

AlphaMissense predicts likely benign (score 0.2589) — an in-silico prediction, not a clinical call.

DMD p.Arg2263Cys

c.6787C>T · rs200045725 · VCV499301

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, eas)

Conditions

Becker muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2589	likely benign
REVEL	0.316	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	28.9	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 0.00593% East Asian · 2/33,727 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000496% 6/1,209,203 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00593%	16,863
African / African-American	0.00351%	28,492
Remaining individualsnot grpmax-eligible	0.0021%	47,579
European (non-Finnish)	0.000112%	895,079

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.Arg2263Cys
Coding: c.6787C>T
MANE Select: NM_004006
dbSNP: rs200045725
Type: single nucleotide variant
Location: chrX:31929721 (GRCh38)

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

Disease context

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

Also linked: cardiomyopathy dilated cardiomyopathy 3B Duchenne muscular dystrophy

For Becker muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

DMD p.Arg2263His Likely benign ★★ same residue
DMD p.Arg2263= 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-arg2263cys (accessed [today's date]).

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