Is EMD p.Ser8Trp (c.23C>G) pathogenic?

EMD p.Ser8Trp (c.23C>G) is classified Conflicting classifications of pathogenicity in EMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-12-21). AlphaMissense: likely pathogenic (0.9021); Absent from gnomAD v4.1; Associated with EMD-related disorders.

What condition is associated with EMD p.Ser8Trp (c.23C>G)?

EMD p.Ser8Trp (c.23C>G) is associated with EMD-related disorders, X-linked Emery-Dreifuss muscular dystrophy, cardiomyopathy, dilated, 3C (ClinVar).

How common is EMD p.Ser8Trp (c.23C>G) in the general population?

EMD p.Ser8Trp (c.23C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMD p.Ser8Trp (c.23C>G)?

AlphaMissense predicts likely pathogenic (score 0.9021) — an in-silico prediction, not a clinical call.

EMD p.Ser8Trp

c.23C>G · rs869025400 · VCV222597

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9021 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

EMD-related disorders

Computational evidence

Protein change
AlphaMissense	0.9021	likely pathogenic · top 4% in EMD
REVEL	0.398	indeterminate
SaProt	LLR -14.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,709 bp · p 0.47 · regional, not allelic
Overall
CADD	25.1	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.Ser8Trp
Coding: c.23C>G
MANE Select: NM_000117
dbSNP: rs869025400
Type: single nucleotide variant
Location: chrX:154379507 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 8: the lem domain; a UniProt-annotated variant site (in cmd3c; uncertain significance); a modified residue (phosphoserine)

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

Disease context

EMD-related disorders

Also linked: X-linked Emery-Dreifuss muscular dystrophy cardiomyopathy, dilated, 3C

Similar variants

EMD p.Ser8Leu 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
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-ser8trp (accessed [today's date]).

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