Is SGCE p.Leu35Pro (c.104T>C) pathogenic?

SGCE p.Leu35Pro (c.104T>C) is classified Uncertain significance in SGCE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.2821); Absent from gnomAD v4.1; Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Leu35Pro (c.104T>C)?

SGCE p.Leu35Pro (c.104T>C) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Leu35Pro (c.104T>C) in the general population?

SGCE p.Leu35Pro (c.104T>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.Leu35Pro (c.104T>C)?

AlphaMissense predicts likely benign (score 0.2821) — an in-silico prediction, not a clinical call.

SGCE p.Leu35Pro

c.104T>C · rs2117137538 · VCV1478230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2821 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,850)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
AlphaMissense	0.2821	likely benign
REVEL	0.611	indeterminate
SaProt	LLR -11.05	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 71 kb · p 0.00058 · regional, not allelic
Overall
CADD	23.5	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

No allele count reported in gnomAD v4.1 (AN 1,602,850). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SGCE
Protein: p.Leu35Pro
Coding: c.104T>C
MANE Select: NM_003919
dbSNP: rs2117137538
Type: single nucleotide variant
Location: chr7:94655995 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.32 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.19

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)

Similar variants

SGCE p.Leu35= Likely benign ★ same residue
SGCE c.109+1G>A Pathogenic ★★ same condition
SGCE c.109+2T>C Pathogenic ★★ same condition
SGCE p.Arg23Cys Uncertain significance ★★ ⚠ same condition
SGCE p.Gly19Ser Uncertain significance ★★ ⚠ same condition
SGCE p.Ile199Met Uncertain significance ★★ same condition
SGCE p.Pro4Ser Uncertain significance ★★ ⚠ same condition
SGCE p.Thr32Ala Uncertain significance ★★ ⚠ same condition

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-leu35pro (accessed [today's date]).

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