Is DMD p.Pro3668Arg (c.11003C>G) pathogenic?

DMD p.Pro3668Arg (c.11003C>G) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-17). AlphaMissense: likely pathogenic (0.6121); Very rare (popmax 0.00887%, eas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Pro3668Arg (c.11003C>G)?

DMD p.Pro3668Arg (c.11003C>G) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Pro3668Arg (c.11003C>G) in the general population?

DMD p.Pro3668Arg (c.11003C>G) is very rare (popmax 0.00887%, eas) (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.Pro3668Arg (c.11003C>G)?

AlphaMissense predicts likely pathogenic (score 0.6121) — an in-silico prediction, not a clinical call.

DMD p.Pro3668Arg

c.11003C>G · rs2147774126 · VCV1417940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00887%, eas)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.6121	likely pathogenic
REVEL	0.433	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 3.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 25 kb · p 0.27 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00887% East Asian · 3/33,808 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.00033% 4/1,210,590 alleles · very rare exomes 4/1,097,047 · genomes 0/113,543 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00887%	11,269
Remaining individualsnot grpmax-eligible	0.0021%	47,621

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.Pro3668Arg
Coding: c.11003C>G
MANE Select: NM_004006
dbSNP: rs2147774126
Type: single nucleotide variant
Location: chrX:31134113 (GRCh38)
Residue 3668: the 'disordered' region

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

For Duchenne muscular dystrophy (Orphanet):

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

Similar variants

DMD p.Pro3668Ser 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-pro3668arg (accessed [today's date]).

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