Is EMD p.His23Pro (c.68_69delinsCT) pathogenic?

EMD p.His23Pro (c.6869delinsCT) is classified Uncertain significance in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). Absent from gnomAD; Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.His23Pro (c.68_69delinsCT)?

EMD p.His23Pro (c.68_69delinsCT) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.His23Pro (c.68_69delinsCT) in the general population?

EMD p.His23Pro (c.68_69delinsCT) is absent from gnomAD (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.His23Pro

c.68_69delinsCT · rs2067873549 · VCV834387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.His23Pro
Coding: c.68_69delinsCT
MANE Select: NM_000117
dbSNP: rs2067873549
Type: Indel
Location: chrX:154379552 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 23: the lem domain

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.His23= Likely benign ★★ same residue
EMD p.His23Gln Uncertain significance ★ ⚠ same residue
EMD p.Lys37Ile Uncertain significance ★★ same condition
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-his23pro (accessed [today's date]).

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