Is DMD p.Cys3153Ser (c.9457T>A) pathogenic?

DMD p.Cys3153Ser (c.9457T>A) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely benign (0.2768); Very rare (popmax 0.000112%, nfe); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Cys3153Ser (c.9457T>A)?

DMD p.Cys3153Ser (c.9457T>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Cys3153Ser (c.9457T>A) in the general population?

DMD p.Cys3153Ser (c.9457T>A) 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.Cys3153Ser (c.9457T>A)?

AlphaMissense predicts likely benign (score 0.2768) — an in-silico prediction, not a clinical call.

DMD p.Cys3153Ser

c.9457T>A · VCV3634792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2768	likely benign
REVEL	0.691	pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 170 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	25.5	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) · 1/895,363 alleles

Overall 9.11e-05% 1/1,097,981 alleles · very rare

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.Cys3153Ser
Coding: c.9457T>A
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:31209604 (GRCh38)
Residue 3153: an α-helix; the 'interaction with synm' 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.Cys3153Phe Likely benign ★ same residue
DMD p.Cys3153fs Pathogenic/Likely 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
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-cys3153ser (accessed [today's date]).

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