Is SGCE p.Arg237Ter (c.709C>T) pathogenic?

SGCE p.Arg237Ter (c.709C>T) is classified Pathogenic in SGCE (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-16). Very rare (popmax 8.48e-05%, nfe); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Arg237Ter (c.709C>T)?

SGCE p.Arg237Ter (c.709C>T) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Arg237Ter (c.709C>T) in the general population?

SGCE p.Arg237Ter (c.709C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Myoclonus-dystonia syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SGCE p.Arg237Ter

c.709C>T · rs398123812 · VCV94384

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.24	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 10	GERP 0.92, phastCons 1
Overall
CADD	40.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,320 alleles

Overall 6.84e-05% 1/1,460,956 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: SGCE
Protein: p.Arg237Ter
Coding: c.709C>T
MANE Select: NM_022900 · reported on NM_003919
dbSNP: rs398123812
Type: single nucleotide variant
Location: chr7:94603406 (GRCh38)

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

Disease context

myoclonic dystonia 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Myoclonus-dystonia syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

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/sgce-p-arg237ter (accessed [today's date]).

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