Is EMD p.Ser120Ter (c.359C>A) pathogenic?

EMD p.Ser120Ter (c.359C>A) is classified Likely pathogenic in EMD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). Absent from gnomAD v4.1; Associated with Emery-Dreifuss muscular dystrophy 1, X-linked.

What condition is associated with EMD p.Ser120Ter (c.359C>A)?

EMD p.Ser120Ter (c.359C>A) is associated with Emery-Dreifuss muscular dystrophy 1, X-linked (ClinVar).

How common is EMD p.Ser120Ter (c.359C>A) in the general population?

EMD p.Ser120Ter (c.359C>A) is absent from gnomAD v4.1 (gnomAD).

EMD p.Ser120Ter

c.359C>A · VCV3896858

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,211,616)

Conditions

Emery-Dreifuss muscular dystrophy 1, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	Δ0.85	donor gain · deltas
Pangolin	Δ0.54	gain · loss 0.32 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.2	GERP 0.28, phastCons 0.002
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,211,616). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMD
Protein: p.Ser120Ter
Coding: c.359C>A
MANE Select: NM_000117
Type: single nucleotide variant
Location: chrX:154380327 (GRCh38)
Structure: AlphaFold pLDDT 61.26 · 6 PDB
Residue 120: the 'interaction with f-actin' region

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.Ser120Leu Uncertain significance ★★ ⚠ 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
EMD p.Arg204Cys 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-ser120ter (accessed [today's date]).

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