Is EMD p.Pro183His (c.548C>A) pathogenic?

EMD p.Pro183His (c.548C>A) is classified Pathogenic in EMD (ClinVar, Single submitter, 2 submitters; last evaluated 2019-09-28). AlphaMissense: likely benign (0.2292); Absent from gnomAD v4.1; Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Pro183His (c.548C>A)?

EMD p.Pro183His (c.548C>A) is associated with X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Pro183His (c.548C>A) in the general population?

EMD p.Pro183His (c.548C>A) is absent from gnomAD v4.1 (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.Pro183His (c.548C>A)?

AlphaMissense predicts likely benign (score 0.2292) — an in-silico prediction, not a clinical call.

EMD p.Pro183His

c.548C>A · rs104894805 · VCV11178

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2292 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.2292	likely benign ⚠ discordant with ClinVar
REVEL	0.525	indeterminate
SaProt	LLR -9.02	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 4.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	21.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EMD
Protein: p.Pro183His
Coding: c.548C>A
MANE Select: NM_000117
dbSNP: rs104894805
Type: single nucleotide variant
Location: chrX:154380980 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 183: a UniProt-annotated variant site (in edmd1; likely pathogenic; no loss of binding to f-actin; enhanced rate of actin polymerization); a UniProt-annotated variant site (in edmd1; likely pathogenic); the 'interaction with f-actin' region; the 'interaction with ctnnb1' 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

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.Pro183= Conflicting classifications of pathogenicity ★ same residue
EMD p.Pro183Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Pro183Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Pro183Thr Pathogenic ⚠ same residue
EMD p.Pro183Arg 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

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-pro183his (accessed [today's date]).

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