Is EMD p.Ser54Phe (c.161C>T) pathogenic?

EMD p.Ser54Phe (c.161C>T) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.1555); Very rare (popmax 0.000112%, nfe); Associated with Emery-Dreifuss muscular dystrophy 1, X-linked.

What condition is associated with EMD p.Ser54Phe (c.161C>T)?

EMD p.Ser54Phe (c.161C>T) is associated with Emery-Dreifuss muscular dystrophy 1, X-linked (ClinVar).

How common is EMD p.Ser54Phe (c.161C>T) in the general population?

EMD p.Ser54Phe (c.161C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about EMD p.Ser54Phe (c.161C>T)?

AlphaMissense predicts likely benign (score 0.1555) — an in-silico prediction, not a clinical call.

EMD p.Ser54Phe

c.161C>T · rs782764813 · VCV2675026

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Emery-Dreifuss muscular dystrophy 1, X-linked

Computational evidence

Protein change
AlphaMissense	0.1555	likely benign
REVEL	0.601	indeterminate
SaProt	LLR -8.37	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 6.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	18.74	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) · 1/892,863 alleles

Overall 9.16e-05% 1/1,092,198 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.Ser54Phe
Coding: c.161C>T
MANE Select: NM_000117
dbSNP: rs782764813
Type: single nucleotide variant
Location: chrX:154379768 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 54: a UniProt-annotated variant site (in edmd1; likely pathogenic; unable to rescue impaired differentiation of emd-deficient myogenic progenitor cells; no loss of binding to f-actin; enhanced rate of actin polymerization and loss of binding to bclaf1); the 'interaction with f-actin' region; a modified residue (phosphoserine)

Full EMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Emery-Dreifuss muscular dystrophy 1, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EMD p.Ser54Cys Uncertain significance ★ ⚠ same residue
EMD p.Ser54= Likely benign ★ same residue
EMD c.265+1G>A Likely pathogenic ★★ same condition
EMD c.450-2A>G Pathogenic/Likely pathogenic ★★ same condition
EMD p.Gln44Ter Pathogenic ★★ same condition
EMD c.82+3A>G Uncertain significance ★★ same condition
EMD p.Ala55Ser Uncertain significance ★★ ⚠ same condition
EMD p.Arg152His Uncertain significance ★★ ⚠ 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-ser54phe (accessed [today's date]).

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