Is EMD p.Gln44Ter (c.130C>T) pathogenic?

EMD p.Gln44Ter (c.130C>T) is classified Pathogenic in EMD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-26). Very rare (popmax 0.000112%, nfe); Associated with Emery-Dreifuss muscular dystrophy 1, X-linked.

What condition is associated with EMD p.Gln44Ter (c.130C>T)?

EMD p.Gln44Ter (c.130C>T) is associated with Emery-Dreifuss muscular dystrophy 1, X-linked, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Gln44Ter (c.130C>T) in the general population?

EMD p.Gln44Ter (c.130C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

EMD p.Gln44Ter

c.130C>T · rs132630262 · VCV11176

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Emery-Dreifuss muscular dystrophy 1, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.2, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,804 alleles

Overall 9.13e-05% 1/1,095,454 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: EMD
Protein: p.Gln44Ter
Coding: c.130C>T
MANE Select: NM_000117
dbSNP: rs132630262
Type: single nucleotide variant
Location: chrX:154379737 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 44: the lem domain

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

Disease context

Emery-Dreifuss muscular dystrophy 1, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Gln44= Likely benign ★ same residue
EMD c.187+1G>A Pathogenic ★★ same condition
EMD c.187+1G>T Pathogenic/Likely pathogenic ★★ same condition
EMD c.265+1G>A Likely pathogenic ★★ same condition
EMD c.266-2A>G Pathogenic ★★ same condition
EMD c.266-3A>G Pathogenic ★★ same condition
EMD c.399+1G>T Pathogenic ★★ same condition
EMD c.399+2T>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/emd-p-gln44ter (accessed [today's date]).

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