Is EMD p.Met1Arg (c.2T>G) pathogenic?

EMD p.Met1Arg (c.2T>G) is classified Pathogenic in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-02). Absent from gnomAD v4.1; Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Met1Arg (c.2T>G)?

EMD p.Met1Arg (c.2T>G) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Met1Arg (c.2T>G) in the general population?

EMD p.Met1Arg (c.2T>G) is absent from gnomAD v4.1 (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.Met1Arg

c.2T>G · rs2148127941 · VCV1074958

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	start-loss	predicted loss-of-function
REVEL	0.809	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.4, phastCons 1
Overall
CADD	20.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EMD
Protein: p.Met1Arg
Coding: c.2T>G
MANE Select: NM_000117
dbSNP: rs2148127941
Type: single nucleotide variant
Location: chrX:154379486 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 1: the lem domain; a modified residue (n-acetylmethionine)

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.Met1Ile Pathogenic ★★ same residue
EMD p.Met1Val Pathogenic ★★ same residue
EMD p.Met1Thr Pathogenic ★ 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

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-met1arg (accessed [today's date]).

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