Is AOPEP p.Arg230fs (c.687_688dup) pathogenic?

AOPEP p.Arg230fs (c.687688dup) is classified Likely pathogenic in AOPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). Associated with dystonia 31.

What condition is associated with AOPEP p.Arg230fs (c.687_688dup)?

AOPEP p.Arg230fs (c.687_688dup) is associated with dystonia 31 (ClinVar).

AOPEP p.Arg230fs

c.687_688dup · VCV4850483

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dystonia 31

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AOPEP
Protein: p.Arg230fs
Coding: c.687_688dup
MANE Select: NM_001193329
Type: Duplication
Location: chr9:94760469 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.36

Full AOPEP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonia 31 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FANCC p.Lys230Glu Uncertain significance ★★ ⚠ same residue
AOPEP p.Tyr736Ter Likely pathogenic ★ same condition
FANCC p.Lys230= Conflicting classifications of pathogenicity ★ same residue
FANCC p.Lys230Arg Uncertain significance ★ ⚠ same residue
FANCC p.Lys230Thr Uncertain significance ★ same residue
AOPEP p.Gln235Ter Likely pathogenic ★★ same condition
AOPEP p.Arg401Trp Uncertain significance ★★ ⚠ same condition
AOPEP c.964+2T>G Pathogenic ★ 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/aopep-p-arg230fs (accessed [today's date]).

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