Is SGCE p.Pro75Ala (c.223C>G) pathogenic?

SGCE p.Pro75Ala (c.223C>G) is classified Uncertain significance in SGCE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-12). AlphaMissense: likely benign (0.0942); Very rare (popmax 0.00668%, amr); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Pro75Ala (c.223C>G)?

SGCE p.Pro75Ala (c.223C>G) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Pro75Ala (c.223C>G) in the general population?

SGCE p.Pro75Ala (c.223C>G) is very rare (popmax 0.00668%, amr) (gnomAD).

How is Myoclonus-dystonia syndrome inherited?

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

What do computational predictors say about SGCE p.Pro75Ala (c.223C>G)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

SGCE p.Pro75Ala

c.223C>G · VCV3712070

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.0942	likely benign
REVEL	0.682	pathogenic-leaning
SaProt	LLR -6.08	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 71 kb · p 0.00058 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% Admixed American · 4/59,870 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,610,896 alleles · very rare exomes 4/1,459,126 · genomes 0/151,770 · joint denominator

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.Pro75Ala
Coding: c.223C>G
MANE Select: NM_003919
Type: single nucleotide variant
Location: chr7:94629728 (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-pro75ala (accessed [today's date]).

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