Is ACO2 p.Arg633fs (c.1823_1896dup) pathogenic?

ACO2 p.Arg633fs (c.18231896dup) is classified Likely pathogenic in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-23). Absent from gnomAD; Associated with optic atrophy 9.

What condition is associated with ACO2 p.Arg633fs (c.1823_1896dup)?

ACO2 p.Arg633fs (c.1823_1896dup) is associated with optic atrophy 9 (ClinVar).

How common is ACO2 p.Arg633fs (c.1823_1896dup) in the general population?

ACO2 p.Arg633fs (c.1823_1896dup) is absent from gnomAD (gnomAD).

ACO2 p.Arg633fs

c.1823_1896dup · rs2518236207 · VCV1709577

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

optic atrophy 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: ACO2
Protein: p.Arg633fs
Coding: c.1823_1896dup
MANE Select: NM_001098
dbSNP: rs2518236207
Type: Duplication
Location: chr22:41526316 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 95.44

Full ACO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

optic atrophy 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACO2 p.Arg633Leu Uncertain significance ★★ ⚠ same residue
ACO2 p.Ile752fs Pathogenic ★ same condition
ACO2 p.Arg633Cys Uncertain significance ★ ⚠ same residue
ACO2 p.Arg633His Uncertain significance ★ ⚠ same residue
ACO2 p.Arg633= Likely benign ★ same residue
ACO2 p.Gly419fs Pathogenic same condition
ACO2 p.Gly503Ter Pathogenic ★★ same condition
ACO2 p.Arg684Gln 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/aco2-p-arg633fs (accessed [today's date]).

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