Is DMD p.Thr409Ser (c.1225A>T) pathogenic?

DMD p.Thr409Ser (c.1225A>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0773); Low-frequency (popmax 3.52%, afr); Associated with dilated cardiomyopathy 3B.

What condition is associated with DMD p.Thr409Ser (c.1225A>T)?

DMD p.Thr409Ser (c.1225A>T) is associated with dilated cardiomyopathy 3B, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is DMD p.Thr409Ser (c.1225A>T) in the general population?

DMD p.Thr409Ser (c.1225A>T) is low-frequency (popmax 3.52%, afr) (gnomAD).

What do computational predictors say about DMD p.Thr409Ser (c.1225A>T)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

DMD p.Thr409Ser

c.1225A>T · rs34155804 · VCV94453

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.52%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

dilated cardiomyopathy 3B

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.027	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -4.5, phastCons 0.054
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	4.761	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 3.52% African / African-American · 2,012/57,121 alleles

Filtering AF 3.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.34%

Overall 0.193% 2,334/1,209,415 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.52%	28
Remaining individualsnot grpmax-eligible	0.269%	372
Admixed American	0.247%	404
Middle Eastern	0.161%	622
European (non-Finnish)	0.00793%	12,602
South Asian	0.00528%	18,936

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.Thr409Ser
Coding: c.1225A>T
MANE Select: NM_004006
dbSNP: rs34155804
Type: single nucleotide variant
Location: chrX:32644238 (GRCh38)
Residue 409: an α-helix; a UniProt-annotated variant site (in)

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

Disease context

dilated cardiomyopathy 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Thr409= Likely benign ★★ same residue
DMD p.Thr409Ala 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-thr409ser (accessed [today's date]).

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