Is SGCE p.Pro212= (c.636A>G) pathogenic?

SGCE p.Pro212= (c.636A>G) is classified Benign in SGCE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Ultra-rare (popmax 0.0357%, eas); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Pro212= (c.636A>G)?

SGCE p.Pro212= (c.636A>G) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Pro212= (c.636A>G) in the general population?

SGCE p.Pro212= (c.636A>G) is ultra-rare (popmax 0.0357%, eas) (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.Pro212=

c.636A>G · rs750280111 · VCV2956612

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -11	GERP -3.8
Overall
CADD	1.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% East Asian · 16/44,876 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00105% 17/1,613,898 alleles · ultra-rare exomes 11/1,461,720 · genomes 6/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,805
European (non-Finnish)	8.47e-05%	1,179,956

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.Pro212=
Coding: c.636A>G
MANE Select: NM_003919
dbSNP: rs750280111
Type: single nucleotide variant
Location: chr7:94618784 (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-pro212 (accessed [today's date]).

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