Is EMD p.Trp200Arg (c.598T>C) pathogenic?

EMD p.Trp200Arg (c.598T>C) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-04). AlphaMissense: likely pathogenic (0.5775); Very rare (popmax 0.00547%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Trp200Arg (c.598T>C)?

EMD p.Trp200Arg (c.598T>C) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Trp200Arg (c.598T>C) in the general population?

EMD p.Trp200Arg (c.598T>C) is very rare (popmax 0.00547%, nfe) (gnomAD).

What do computational predictors say about EMD p.Trp200Arg (c.598T>C)?

AlphaMissense predicts likely pathogenic (score 0.5775) — an in-silico prediction, not a clinical call.

EMD p.Trp200Arg

c.598T>C · rs374981936 · VCV163404

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00547%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5775	likely pathogenic
REVEL	0.37	indeterminate
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.60 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	22.7	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 0.00547% European (non-Finnish) · 49/895,247 alleles

Filtering AF 0.00419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.00421% 51/1,210,525 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00547%	18,270
African / African-American	0.00348%	28,695

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.Trp200Arg
Coding: c.598T>C
MANE Select: NM_000117
dbSNP: rs374981936
Type: single nucleotide variant
Location: chrX:154381030 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 200: 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.Trp200Ter Pathogenic/Likely pathogenic ★★ same residue
EMD p.Trp200Leu 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
EMD c.399+1G>T 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-trp200arg (accessed [today's date]).

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