Is SGCE p.Pro72Ser (c.214C>T) pathogenic?

SGCE p.Pro72Ser (c.214C>T) is classified Uncertain significance in SGCE (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-03). AlphaMissense: ambiguous (0.4534); Very rare (popmax 0.0011%, sas); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Pro72Ser (c.214C>T)?

SGCE p.Pro72Ser (c.214C>T) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Pro72Ser (c.214C>T) in the general population?

SGCE p.Pro72Ser (c.214C>T) is very rare (popmax 0.0011%, sas) (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.Pro72Ser (c.214C>T)?

AlphaMissense predicts ambiguous (score 0.4534) — an in-silico prediction, not a clinical call.

SGCE p.Pro72Ser

c.214C>T · VCV4711568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
AlphaMissense	0.4534	ambiguous
REVEL	0.602	indeterminate
SaProt	LLR -8.44	tolerated
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	28.8	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 0.0011% South Asian · 1/91,004 alleles

Overall 6.85e-05% 1/1,459,294 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.Pro72Ser
Coding: c.214C>T
MANE Select: NM_003919
Type: single nucleotide variant
Location: chr7:94629737 (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-pro72ser (accessed [today's date]).

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