Is EMD p.Phe39del (c.115_117del) pathogenic?

EMD p.Phe39del (c.115117del) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-16). Very rare (popmax 0.00268%, nfe); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Phe39del (c.115_117del)?

EMD p.Phe39del (c.115_117del) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Phe39del (c.115_117del) in the general population?

EMD p.Phe39del (c.115_117del) is very rare (popmax 0.00268%, nfe) (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.Phe39del

c.115_117del · rs781959238 · VCV201782

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00268%, nfe)

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 10	GERP 1.2, phastCons 1
Overall
CADD	18.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% European (non-Finnish) · 24/894,511 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00152%

Overall 0.00207% 25/1,207,766 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00268%	37,271
Remaining individualsnot grpmax-eligible	0.0021%	47,534

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EMD
Protein: p.Phe39del
Coding: c.115_117del
MANE Select: NM_000117
dbSNP: rs781959238
Type: Deletion
Location: chrX:154379720 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 39: 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.Phe39fs Pathogenic ★★ same residue
EMD p.Phe39= Likely benign ★★ same residue
EMD p.Asn20fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Leu225fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Leu84fs Pathogenic ★★ same condition
EMD p.Pro208fs Pathogenic ★★ same condition
EMD p.Ser52fs Pathogenic ★★ same condition
EMD p.Tyr41fs 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-phe39del (accessed [today's date]).

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