Is EMD p.Gln222fs (c.662_663insT) pathogenic?

EMD p.Gln222fs (c.662663insT) is classified Likely pathogenic in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). Absent from gnomAD; Associated with Emery-Dreifuss muscular dystrophy 1, X-linked.

What condition is associated with EMD p.Gln222fs (c.662_663insT)?

EMD p.Gln222fs (c.662_663insT) is associated with Emery-Dreifuss muscular dystrophy 1, X-linked (ClinVar).

How common is EMD p.Gln222fs (c.662_663insT) in the general population?

EMD p.Gln222fs (c.662_663insT) is absent from gnomAD (gnomAD).

EMD p.Gln222fs

c.662_663insT · rs2522790651 · VCV3069158

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP -0.75, phastCons 1

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

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.Gln222fs
Coding: c.662_663insT
MANE Select: NM_000117
dbSNP: rs2522790651
Type: Insertion
Location: chrX:154381094 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 222: the 'interaction with f-actin' region

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

Similar variants

EMD p.Gln222His Uncertain significance ★ ⚠ same residue
EMD c.265+1G>A Likely pathogenic ★★ same condition
EMD c.450-2A>G Pathogenic/Likely pathogenic ★★ same condition
EMD p.Asn20fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Gln44Ter Pathogenic ★★ same condition
EMD p.Leu225fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Leu84fs Pathogenic ★★ same condition
EMD p.Phe39fs 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-gln222fs (accessed [today's date]).

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