Is EMD p.Arg207Pro (c.620G>C) pathogenic?

EMD p.Arg207Pro (c.620G>C) is classified Benign in EMD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-28). AlphaMissense: likely pathogenic (0.6188); Ultra-rare (popmax 0.0824%, sas); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Arg207Pro (c.620G>C)?

EMD p.Arg207Pro (c.620G>C) is associated with X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Arg207Pro (c.620G>C) in the general population?

EMD p.Arg207Pro (c.620G>C) is ultra-rare (popmax 0.0824%, sas) (gnomAD).

How is Emery-Dreifuss muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EMD p.Arg207Pro (c.620G>C)?

AlphaMissense predicts likely pathogenic (score 0.6188) — an in-silico prediction, not a clinical call.

EMD p.Arg207Pro

c.620G>C · rs782352489 · VCV659968

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6188 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.6188	likely pathogenic
REVEL	0.537	indeterminate
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0824% South Asian · 47/57,006 alleles

Filtering AF 0.0637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.057%

Overall 0.00437% 48/1,098,083 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0824%	1,213
Remaining individualsnot grpmax-eligible	0.0021%	47,657

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.Arg207Pro
Coding: c.620G>C
MANE Select: NM_000117
dbSNP: rs782352489
Type: single nucleotide variant
Location: chrX:154381052 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 207: the 'interaction with f-actin' 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

Also linked: Emery-Dreifuss muscular dystrophy

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.Arg207Gln Uncertain significance ★★ ⚠ same residue
EMD p.Arg207Trp Uncertain significance ★★ ⚠ same residue
EMD p.Arg207fs Pathogenic ★ same residue
EMD p.Arg207= Likely benign ★ 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

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-arg207pro (accessed [today's date]).

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