Is DMD p.Arg563Ser (c.1687C>A) pathogenic?

DMD p.Arg563Ser (c.1687C>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.2033); Ultra-rare (popmax 0.0121%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg563Ser (c.1687C>A)?

DMD p.Arg563Ser (c.1687C>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 3B, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg563Ser (c.1687C>A) in the general population?

DMD p.Arg563Ser (c.1687C>A) is ultra-rare (popmax 0.0121%, nfe) (gnomAD).

What do computational predictors say about DMD p.Arg563Ser (c.1687C>A)?

AlphaMissense predicts likely benign (score 0.2033) — an in-silico prediction, not a clinical call.

DMD p.Arg563Ser

c.1687C>A · rs145739725 · VCV285979

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.2033 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2033	likely benign
REVEL	0.035	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 2.2	GERP -0.25, phastCons 0.97
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	21.6	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 0.0121% European (non-Finnish) · 108/894,717 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00948%

Overall 0.00901% 109/1,209,241 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0121%	8,284
African / African-American	0.00175%	57,132

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.Arg563Ser
Coding: c.1687C>A
MANE Select: NM_004006
dbSNP: rs145739725
Type: single nucleotide variant
Location: chrX:32573762 (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: dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

DMD p.Arg563= Likely benign ★★ same residue
DMD p.Arg563Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg563His Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg563fs Pathogenic ★ 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

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-arg563ser (accessed [today's date]).

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