Is DMD p.Thr134= (c.402C>A) pathogenic?

DMD p.Thr134= (c.402C>A) is classified Likely benign in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0178%, eas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Thr134= (c.402C>A)?

DMD p.Thr134= (c.402C>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Thr134= (c.402C>A) in the general population?

DMD p.Thr134= (c.402C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

How is Duchenne muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DMD p.Thr134=

c.402C>A · rs1245288522 · VCV792581

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -1.2, phastCons 1
Overall
CADD	7.469	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 6/33,749 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.000909% 11/1,209,498 alleles · ultra-rare exomes 9/1,097,960 · genomes 2/111,538 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,625
Admixed American	0.00657%	15,225
Remaining individualsnot grpmax-eligible	0.0021%	47,576
African / African-American	0.00175%	57,116

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.Thr134=
Coding: c.402C>A
MANE Select: NM_004006
dbSNP: rs1245288522
Type: single nucleotide variant
Location: chrX:32816596 (GRCh38)
Residue 134: the calponin-homology (ch) 2 domain; the 'actin-binding' 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.Thr134Asn Uncertain significance ★ same residue
DMD p.Thr134fs Pathogenic ★ same residue
DMD p.Thr134Ser 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

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-thr134 (accessed [today's date]).

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