Is EMD p.Arg203His (c.608G>A) pathogenic?

EMD p.Arg203His (c.608G>A) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-11-17). AlphaMissense: likely benign (0.311); Rare (popmax 0.355%, eas); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Arg203His (c.608G>A)?

EMD p.Arg203His (c.608G>A) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Arg203His (c.608G>A) in the general population?

EMD p.Arg203His (c.608G>A) is rare (popmax 0.355%, eas) (gnomAD).

What do computational predictors say about EMD p.Arg203His (c.608G>A)?

AlphaMissense predicts likely benign (score 0.311) — an in-silico prediction, not a clinical call.

EMD p.Arg203His

c.608G>A · rs144842093 · VCV201775

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.311 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.355%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.311	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; 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	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.355% East Asian · 120/33,792 alleles

Filtering AF 0.303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.284%

Overall 0.0112% 136/1,210,488 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.355%	282
Middle Eastern	0.023%	4,355
Remaining individualsnot grpmax-eligible	0.0042%	23,813
European (non-Finnish)	0.00145%	68,867

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.Arg203His
Coding: c.608G>A
MANE Select: NM_000117
dbSNP: rs144842093
Type: single nucleotide variant
Location: chrX:154381040 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 203: the 'interaction with f-actin' region

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 Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Arg203fs Pathogenic ★ 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
EMD c.399+1G>T Pathogenic ★★ same condition
EMD c.399+2T>C 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-arg203his (accessed [today's date]).

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