Is EMD p.Pro183Ser (c.547C>T) pathogenic?

EMD p.Pro183Ser (c.547C>T) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-08). AlphaMissense: likely benign (0.1339); Very rare (popmax 0.000112%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Pro183Ser (c.547C>T)?

EMD p.Pro183Ser (c.547C>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Pro183Ser (c.547C>T) in the general population?

EMD p.Pro183Ser (c.547C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about EMD p.Pro183Ser (c.547C>T)?

AlphaMissense predicts likely benign (score 0.1339) — an in-silico prediction, not a clinical call.

EMD p.Pro183Ser

c.547C>T · rs104894806 · VCV1038252

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1339	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -6.96	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 5.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	16.76	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 0.000112% European (non-Finnish) · 1/895,469 alleles

Overall 9.11e-05% 1/1,097,963 alleles · very rare

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.Pro183Ser
Coding: c.547C>T
MANE Select: NM_000117
dbSNP: rs104894806
Type: single nucleotide variant
Location: chrX:154380979 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked Emery-Dreifuss muscular dystrophy

Similar variants

EMD p.Pro183His Pathogenic ★ ⚠ same residue
EMD p.Pro183= Conflicting classifications of pathogenicity ★ same residue
EMD p.Pro183Arg Uncertain significance ★ ⚠ same residue
EMD p.Pro183Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EMD p.Pro183Thr 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

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-pro183ser (accessed [today's date]).

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