Is SGCE p.Trp7Arg (c.19T>C) pathogenic?

SGCE p.Trp7Arg (c.19T>C) is classified Uncertain significance in SGCE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-21). AlphaMissense: ambiguous (0.3412); Very rare (popmax 0.00134%, afr); Associated with myoclonic dystonia 11.

What condition is associated with SGCE p.Trp7Arg (c.19T>C)?

SGCE p.Trp7Arg (c.19T>C) is associated with myoclonic dystonia 11 (ClinVar).

How common is SGCE p.Trp7Arg (c.19T>C) in the general population?

SGCE p.Trp7Arg (c.19T>C) is very rare (popmax 0.00134%, afr) (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.Trp7Arg (c.19T>C)?

AlphaMissense predicts ambiguous (score 0.3412) — an in-silico prediction, not a clinical call.

SGCE p.Trp7Arg

c.19T>C · rs1271444866 · VCV912151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

myoclonic dystonia 11

Computational evidence

Protein change
AlphaMissense	0.3412	ambiguous
REVEL	0.577	indeterminate
SaProt	LLR -4.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 71 kb · p 0.00058 · regional, not allelic
Overall
CADD	23.0	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 0.00134% African / African-American · 1/74,822 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000475%

Overall 0.000869% 14/1,610,904 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,822
European (non-Finnish)	0.0011%	90,566

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.Trp7Arg
Coding: c.19T>C
MANE Select: NM_003919
dbSNP: rs1271444866
Type: single nucleotide variant
Location: chr7:94656080 (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.Trp7Cys Uncertain significance ★ same residue
SGCE p.Trp7Ter Conflicting classifications of pathogenicity ★ ⚠ 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

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-trp7arg (accessed [today's date]).

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