Is EMD p.Pro169fs (c.506_507del) pathogenic?

EMD p.Pro169fs (c.506507del) is classified Pathogenic in EMD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-15). Very rare (popmax 0.00175%, afr); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Pro169fs (c.506_507del)?

EMD p.Pro169fs (c.506_507del) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Pro169fs (c.506_507del) in the general population?

EMD p.Pro169fs (c.506_507del) is very rare (popmax 0.00175%, afr) (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.Pro169fs

c.506_507del · rs1422834817 · VCV11171

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

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	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 4.4	GERP 1.6, phastCons 1
Overall
CADD	24.2	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

Grpmax group 0.00175% African / African-American · 1/57,137 alleles

Overall 0.000165% 2/1,209,797 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00175%	57,137
European (non-Finnish)	0.000112%	895,127

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.Pro169fs
Coding: c.506_507del
MANE Select: NM_000117
dbSNP: rs1422834817
Type: Deletion
Location: chrX:154380938 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 169: the 'interaction with f-actin' region; the 'interaction with ctnnb1' region

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.Asn20fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Leu225fs Pathogenic/Likely pathogenic ★★ same condition
EMD p.Leu84fs Pathogenic ★★ same condition
EMD p.Phe39fs Pathogenic ★★ same condition
EMD p.Pro208fs Pathogenic ★★ same condition
EMD p.Ser52fs Pathogenic ★★ same condition
EMD p.Tyr41fs Pathogenic ★★ same condition
EMD p.Phe39del Uncertain significance ★★ 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-pro169fs (accessed [today's date]).

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