Is DMD p.Ser3639Pro (c.10915T>C) pathogenic?

DMD p.Ser3639Pro (c.10915T>C) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1961); Very rare (popmax 0.00173%, afr); Associated with Becker muscular dystrophy.

What condition is associated with DMD p.Ser3639Pro (c.10915T>C)?

DMD p.Ser3639Pro (c.10915T>C) is associated with Becker muscular dystrophy, dilated cardiomyopathy 3B, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Ser3639Pro (c.10915T>C) in the general population?

DMD p.Ser3639Pro (c.10915T>C) is very rare (popmax 0.00173%, afr) (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.Ser3639Pro (c.10915T>C)?

AlphaMissense predicts likely benign (score 0.1961) — an in-silico prediction, not a clinical call.

DMD p.Ser3639Pro

c.10915T>C · rs990606875 · VCV1519466

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Becker muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1961	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 3.3, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 25 kb · p 0.27 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,801 alleles

Overall 8.26e-05% 1/1,210,935 alleles · very rare exomes 1/1,097,175 · genomes 0/113,760 · 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.Ser3639Pro
Coding: c.10915T>C
MANE Select: NM_004006
dbSNP: rs990606875
Type: single nucleotide variant
Location: chrX:31146297 (GRCh38)
Residue 3639: the 'disordered' region

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: 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.Ser3639Phe 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-ser3639pro (accessed [today's date]).

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