Is EMD p.Arg152His (c.455G>A) pathogenic?

EMD p.Arg152His (c.455G>A) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00218%, amr); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Arg152His (c.455G>A)?

EMD p.Arg152His (c.455G>A) is associated with X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy 1, X-linked (ClinVar).

How common is EMD p.Arg152His (c.455G>A) in the general population?

EMD p.Arg152His (c.455G>A) is very rare (popmax 0.00218%, amr) (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.Arg152His (c.455G>A)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

EMD p.Arg152His

c.455G>A · rs782317753 · VCV2441219

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.7, phastCons 0.014
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	17.2	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 0.00218% Admixed American · 1/45,958 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000578% 7/1,210,458 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,958
African / African-American	0.00174%	57,372
European (non-Finnish)	0.000559%	179,049

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.Arg152His
Coding: c.455G>A
MANE Select: NM_000117
dbSNP: rs782317753
Type: single nucleotide variant
Location: chrX:154380887 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 152: 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 1, X-linked

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.Arg152Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Arg152= 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
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-arg152his (accessed [today's date]).

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