Is DMD p.Thr1136Ser (c.3406A>T) pathogenic?

DMD p.Thr1136Ser (c.3406A>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0788); Common (popmax 6.62%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Thr1136Ser (c.3406A>T)?

DMD p.Thr1136Ser (c.3406A>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

What do computational predictors say about DMD p.Thr1136Ser (c.3406A>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

DMD p.Thr1136Ser

Q: How common is DMD p.Thr1136Ser (c.3406A>T) in the general population?

DMD p.Thr1136Ser (c.3406A>T) is common (popmax 6.62%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3406A>T · rs3827462 · VCV94587

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.62%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.056	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 -0.33	GERP -3.9
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	0.244	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 6.62% East Asian · 2,222/33,556 alleles

Filtering AF 6.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.3%

Overall 0.612% 7,384/1,206,084 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	6.62%	15
South Asian	5.06%	20
Finnishnot grpmax-eligible	3.94%	25
Remaining individualsnot grpmax-eligible	0.514%	195
Middle Eastern	0.323%	310
Ashkenazi Jewishnot grpmax-eligible	0.0684%	1,463
European (non-Finnish)	0.0256%	3,902
Admixed American	0.00881%	11,357
African / African-American	0.00877%	11,408

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.Thr1136Ser
Coding: c.3406A>T
MANE Select: NM_004006
dbSNP: rs3827462
Type: single nucleotide variant
Location: chrX:32463465 (GRCh38)
Residue 1136: a UniProt-annotated variant site (in)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy

Similar variants

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
DMD c.10554-2A>G Pathogenic/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-thr1136ser (accessed [today's date]).

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