Is EMD p.Ser193Phe (c.578C>T) pathogenic?

EMD p.Ser193Phe (c.578C>T) is classified Uncertain significance in EMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-22). AlphaMissense: likely benign (0.1799); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with EMD p.Ser193Phe (c.578C>T)?

EMD p.Ser193Phe (c.578C>T) is associated with Cardiovascular phenotype, X-linked Emery-Dreifuss muscular dystrophy (ClinVar).

How common is EMD p.Ser193Phe (c.578C>T) in the general population?

EMD p.Ser193Phe (c.578C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMD p.Ser193Phe (c.578C>T)?

AlphaMissense predicts likely benign (score 0.1799) — an in-silico prediction, not a clinical call.

EMD p.Ser193Phe

c.578C>T · rs1220835396 · VCV1471669

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1799	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -11.93	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	19.66	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.Ser193Phe
Coding: c.578C>T
MANE Select: NM_000117
dbSNP: rs1220835396
Type: single nucleotide variant
Location: chrX:154381010 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 193: 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

Similar variants

EMD p.Ser193= 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
EMD c.399+2T>C 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-ser193phe (accessed [today's date]).

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