Is EMD p.Pro224= (c.672G>A) pathogenic?

EMD p.Pro224= (c.672G>A) is classified Likely benign in EMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-12). Very rare (popmax 0.00888%, eas); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Pro224= (c.672G>A)?

EMD p.Pro224= (c.672G>A) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Pro224= (c.672G>A) in the general population?

EMD p.Pro224= (c.672G>A) is very rare (popmax 0.00888%, eas) (gnomAD).

EMD p.Pro224=

c.672G>A · rs1267603257 · VCV1092006

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00888%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -3
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00888% East Asian · 3/33,792 alleles

Filtering AF 0.00273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.0033% 40/1,210,473 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00888%	11,264
European (non-Finnish)	0.0038%	26,329
African / African-American	0.00349%	28,685
Remaining individualsnot grpmax-eligible	0.0021%	47,606

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.Pro224=
Coding: c.672G>A
MANE Select: NM_000117
dbSNP: rs1267603257
Type: single nucleotide variant
Location: chrX:154381104 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB

Full EMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Pro224Arg Uncertain significance ★★ ⚠ same residue
EMD p.Pro224Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Pro224Ser Uncertain significance ★ 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-pro224 (accessed [today's date]).

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