Is DMD p.Arg3566Cys (c.10696C>T) pathogenic?

DMD p.Arg3566Cys (c.10696C>T) is classified Likely benign in DMD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9853); Very rare (popmax 0.00352%, sas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg3566Cys (c.10696C>T)?

DMD p.Arg3566Cys (c.10696C>T) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg3566Cys (c.10696C>T) in the general population?

DMD p.Arg3566Cys (c.10696C>T) is very rare (popmax 0.00352%, sas) (gnomAD).

How is Duchenne 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.Arg3566Cys (c.10696C>T)?

AlphaMissense predicts likely pathogenic (score 0.9853) — an in-silico prediction, not a clinical call.

DMD p.Arg3566Cys

c.10696C>T · rs750800262 · VCV851421

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00352%, sas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9853	likely pathogenic · top 5% in DMD
REVEL	0.69	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 7.9e-06 · regional, not allelic
Overall
CADD	33.0	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 0.00352% South Asian · 2/56,859 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000364% 4/1,097,943 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00352%	28,430
European (non-Finnish)	0.000223%	447,529

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.Arg3566Cys
Coding: c.10696C>T
MANE Select: NM_004006
dbSNP: rs750800262
Type: single nucleotide variant
Location: chrX:31147376 (GRCh38)

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

Disease context

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

Also linked: cardiomyopathy Becker muscular dystrophy

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Arg3566His Uncertain significance ★★ 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-arg3566cys (accessed [today's date]).

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