Is EMD p.Asp138fs (c.412dup) pathogenic?

EMD p.Asp138fs (c.412dup) is classified Pathogenic in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Asp138fs (c.412dup)?

EMD p.Asp138fs (c.412dup) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EMD p.Asp138fs

c.412dup · VCV4721275

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 38 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -1.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EMD
Protein: p.Asp138fs
Coding: c.412dup
MANE Select: NM_000117
Type: Duplication
Location: chrX:154380764 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 138: the 'interaction with f-actin' region

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

Disease context

X-linked Emery-Dreifuss muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Emery-Dreifuss muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

EMD p.Asp138Asn Uncertain significance ★ ⚠ same residue
EMD p.Asp138Gly Uncertain significance ★ ⚠ same residue
EMD p.Arg46fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Gln133fs Pathogenic ★ same condition
EMD p.Gln219fs Pathogenic ★ same condition
EMD p.Met191fs Pathogenic ★ same condition
EMD p.Phe190fs Pathogenic ★ same condition
EMD p.Ser49fs 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/emd-p-asp138fs (accessed [today's date]).

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