Is SGCE p.Leu321Pro (c.962T>C) pathogenic?

SGCE p.Leu321Pro (c.962T>C) is classified Uncertain significance in SGCE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.9926); Absent from gnomAD v4.1; Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Leu321Pro (c.962T>C)?

SGCE p.Leu321Pro (c.962T>C) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Leu321Pro (c.962T>C) in the general population?

SGCE p.Leu321Pro (c.962T>C) is absent from gnomAD v4.1 (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.Leu321Pro (c.962T>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

SGCE p.Leu321Pro

c.962T>C · rs1799076594 · VCV843449

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -13.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 71 kb · p 0.00058 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SGCE
Protein: p.Leu321Pro
Coding: c.962T>C
MANE Select: NM_003919
dbSNP: rs1799076594
Type: single nucleotide variant
Location: chr7:94600721 (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-leu321pro (accessed [today's date]).

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