Is EMD p.Arg18= (c.52C>A) pathogenic?

EMD p.Arg18= (c.52C>A) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). No allele count reported in gnomAD v4.1 (AN 1,170,818); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Arg18= (c.52C>A)?

EMD p.Arg18= (c.52C>A) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Arg18= (c.52C>A) in the general population?

EMD p.Arg18= (c.52C>A) is no allele count reported in gnomAD v4.1 (AN 1,170,818) (gnomAD).

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.Arg18=

c.52C>A · rs2148127991 · VCV1489618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,818)

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.80	donor gain · deltas
Pangolin	Δ0.66	gain · loss 0.35 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.9	GERP 1.4, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,170,818). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMD
Protein: p.Arg18=
Coding: c.52C>A
MANE Select: NM_000117
dbSNP: rs2148127991
Type: single nucleotide variant
Location: chrX:154379536 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 18: the lem domain; an α-helix

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 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
EMD c.450-2A>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/emd-p-arg18 (accessed [today's date]).

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