Is AOPEP p.Arg493Ter (c.1477C>T) pathogenic?

AOPEP p.Arg493Ter (c.1477C>T) is classified Pathogenic in AOPEP (ClinVar, Single submitter, 2 submitters). Very rare (popmax 0.00863%, amr); Associated with dystonia 31.

What condition is associated with AOPEP p.Arg493Ter (c.1477C>T)?

AOPEP p.Arg493Ter (c.1477C>T) is associated with dystonia 31 (ClinVar).

How common is AOPEP p.Arg493Ter (c.1477C>T) in the general population?

AOPEP p.Arg493Ter (c.1477C>T) is very rare (popmax 0.00863%, amr) (gnomAD).

AOPEP p.Arg493Ter

c.1477C>T · rs577000059 · VCV1319959

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00863%, amr)

Conditions

dystonia 31

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.9, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00863% Admixed American · 4/46,364 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00212% 32/1,512,178 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00863%	11,591
East Asian	0.00529%	18,904
South Asian	0.00255%	39,247
European (non-Finnish)	0.00195%	51,216
Remaining individualsnot grpmax-eligible	0.00171%	58,434
African / African-American	0.0014%	71,414

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: AOPEP
Protein: p.Arg493Ter
Coding: c.1477C>T
MANE Select: NM_001193329
dbSNP: rs577000059
Type: single nucleotide variant
Location: chr9:94924098 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.36
Residue 493: a UniProt-annotated variant site (in dyt31)

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.Asn493Ser Uncertain significance ★ ⚠ same residue
FANCC p.Asn493Thr 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
AOPEP p.Arg255Ter Likely pathogenic ★ same condition
AOPEP p.Trp259Ter Pathogenic same condition
AOPEP p.Arg230fs Likely 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-arg493ter (accessed [today's date]).

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