Is EMD p.Glu11Lys (c.31G>A) pathogenic?

EMD p.Glu11Lys (c.31G>A) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-24). AlphaMissense: ambiguous (0.5566); Absent from gnomAD v4.1; Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Glu11Lys (c.31G>A)?

EMD p.Glu11Lys (c.31G>A) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Glu11Lys (c.31G>A) in the general population?

EMD p.Glu11Lys (c.31G>A) 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.

What do computational predictors say about EMD p.Glu11Lys (c.31G>A)?

AlphaMissense predicts ambiguous (score 0.5566) — an in-silico prediction, not a clinical call.

EMD p.Glu11Lys

c.31G>A · rs2148127965 · VCV1060231

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5566 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,170,622)

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.5566	ambiguous
REVEL	0.422	indeterminate
SaProt	LLR -9.89	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,170,622). 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.Glu11Lys
Coding: c.31G>A
MANE Select: NM_000117
dbSNP: rs2148127965
Type: single nucleotide variant
Location: chrX:154379515 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 11: 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 p.Glu11= Likely benign ★★ same residue
EMD p.Glu11Gly Uncertain significance ★ ⚠ same residue
EMD p.Glu11Asp 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

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-glu11lys (accessed [today's date]).

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