Is ACO2 p.Arg656fs (c.1966_1969del) pathogenic?

ACO2 p.Arg656fs (c.19661969del) is classified Pathogenic in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with infantile cerebellar-retinal degeneration.

What condition is associated with ACO2 p.Arg656fs (c.1966_1969del)?

ACO2 p.Arg656fs (c.1966_1969del) is associated with infantile cerebellar-retinal degeneration (ClinVar).

How common is ACO2 p.Arg656fs (c.1966_1969del) in the general population?

ACO2 p.Arg656fs (c.1966_1969del) is absent from gnomAD (gnomAD).

How is Infantile cerebellar-retinal degeneration inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ACO2 p.Arg656fs

c.1966_1969del · rs1601936467 · VCV803706

Pathogenic Single submitter

Classification

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

infantile cerebellar-retinal degeneration

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 16 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.47, 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.Arg656fs
Coding: c.1966_1969del
MANE Select: NM_001098
dbSNP: rs1601936467
Type: Deletion
Location: chr22:41527300 (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

infantile cerebellar-retinal degeneration — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile cerebellar-retinal degeneration (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ACO2 p.Cys592_Asp595delinsTer Pathogenic ★ same condition
ACO2 p.Lys776fs Pathogenic ★ same condition
ACO2 p.Arg656Ser Uncertain significance ★ ⚠ same residue
ACO2 p.Arg656Thr Uncertain significance ★ ⚠ same residue
ACO2 p.Arg656= Likely benign ★ same residue
ACO2 p.Glu464Ter Pathogenic/Likely pathogenic ★★ same condition
ACO2 p.Ala647Gly Uncertain significance ★★ ⚠ same condition
ACO2 p.Ala768Thr 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-arg656fs (accessed [today's date]).

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