Is DMD p.Pro3547Ser (c.10639C>T) pathogenic?

DMD p.Pro3547Ser (c.10639C>T) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: likely benign (0.2752); Very rare (popmax 0.000112%, nfe); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Pro3547Ser (c.10639C>T)?

DMD p.Pro3547Ser (c.10639C>T) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Pro3547Ser (c.10639C>T) in the general population?

DMD p.Pro3547Ser (c.10639C>T) is very rare (popmax 0.000112%, nfe) (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.Pro3547Ser (c.10639C>T)?

AlphaMissense predicts likely benign (score 0.2752) — an in-silico prediction, not a clinical call.

DMD p.Pro3547Ser

c.10639C>T · rs756033149 · VCV1986888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2752	likely benign
REVEL	0.31	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 8.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 7.9e-06 · regional, not allelic
Overall
CADD	26.6	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 0.000112% European (non-Finnish) · 1/892,268 alleles

Overall 8.3e-05% 1/1,204,388 alleles · very rare exomes 0/1,095,450 · genomes 1/108,938 · joint denominator

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.Pro3547Ser
Coding: c.10639C>T
MANE Select: NM_004006
dbSNP: rs756033149
Type: single nucleotide variant
Location: chrX:31147433 (GRCh38)
Residue 3547: 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.Pro3547= Likely benign ★ same residue
DMD p.Pro3547Leu 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

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-pro3547ser (accessed [today's date]).

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