Is EMD p.Ser194Leu (c.581C>T) pathogenic?

EMD p.Ser194Leu (c.581C>T) is classified Benign in EMD (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-19). AlphaMissense: likely benign (0.1342); Ultra-rare (popmax 0.0211%, sas); Associated with X-linked Emery-Dreifuss muscular dystrophy.

What condition is associated with EMD p.Ser194Leu (c.581C>T)?

EMD p.Ser194Leu (c.581C>T) is associated with X-linked Emery-Dreifuss muscular dystrophy, Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Ser194Leu (c.581C>T) in the general population?

EMD p.Ser194Leu (c.581C>T) is ultra-rare (popmax 0.0211%, sas) (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.Ser194Leu (c.581C>T)?

AlphaMissense predicts likely benign (score 0.1342) — an in-silico prediction, not a clinical call.

EMD p.Ser194Leu

c.581C>T · rs782697057 · VCV966388

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1342 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked Emery-Dreifuss muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1342	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -9.53	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 4.3	GERP 1.6, phastCons 0.33
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	18.49	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 0.0211% South Asian · 12/56,870 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00954%

Overall 0.000991% 12/1,210,454 alleles · ultra-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.Ser194Leu
Coding: c.581C>T
MANE Select: NM_000117
dbSNP: rs782697057
Type: single nucleotide variant
Location: chrX:154381013 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 194: 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

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.Ser194Ter Pathogenic ★ same residue
EMD p.Ser194= Likely benign ★ same residue
EMD p.Ser194fs 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

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-ser194leu (accessed [today's date]).

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