Is SGCE p.Arg372Ter (c.1114C>T) pathogenic?

SGCE p.Arg372Ter (c.1114C>T) is classified Pathogenic in SGCE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-01). Very rare (popmax 0.00134%, afr); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Arg372Ter (c.1114C>T)?

SGCE p.Arg372Ter (c.1114C>T) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Arg372Ter (c.1114C>T) in the general population?

SGCE p.Arg372Ter (c.1114C>T) is very rare (popmax 0.00134%, afr) (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.Arg372Ter

c.1114C>T · rs121908492 · VCV5776

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

myoclonic dystonia 11

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	42.0	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 0.00134% African / African-American · 1/74,898 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,714 alleles · very rare exomes 3/1,461,608 · genomes 1/152,106 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,898
European (non-Finnish)	0.000254%	393,273

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.Arg372Ter
Coding: c.1114C>T
MANE Select: NM_003919
dbSNP: rs121908492
Type: single nucleotide variant
Location: chr7:94598914 (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-arg372ter (accessed [today's date]).

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