Is SGCE p.His45= (c.135C>T) pathogenic?

SGCE p.His45= (c.135C>T) is classified Likely benign in SGCE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-28). Very rare (popmax 0.00334%, amr); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.His45= (c.135C>T)?

SGCE p.His45= (c.135C>T) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.His45= (c.135C>T) in the general population?

SGCE p.His45= (c.135C>T) is very rare (popmax 0.00334%, amr) (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.His45=

c.135C>T · rs1394843820 · VCV1113118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP 1.9, phastCons 1
Overall
CADD	8.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,848 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,610,144 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,924
European (non-Finnish)	8.5e-05%	1,177,074

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.His45=
Coding: c.135C>T
MANE Select: NM_003919
dbSNP: rs1394843820
Type: single nucleotide variant
Location: chr7:94629816 (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-his45 (accessed [today's date]).

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