Is ACO2 p.Gln780fs (c.2338_2339del) pathogenic?

ACO2 p.Gln780fs (c.23382339del) is classified Likely pathogenic in ACO2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-10). Very rare (popmax 8.48e-05%, nfe); Associated with infantile cerebellar-retinal degeneration.

What condition is associated with ACO2 p.Gln780fs (c.2338_2339del)?

ACO2 p.Gln780fs (c.2338_2339del) is associated with infantile cerebellar-retinal degeneration (ClinVar).

How common is ACO2 p.Gln780fs (c.2338_2339del) in the general population?

ACO2 p.Gln780fs (c.2338_2339del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Infantile cerebellar-retinal degeneration inherited?

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

ACO2 p.Gln780fs

c.2338_2339del · rs1114167284 · VCV242873

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,220 alleles

Overall 6.86e-05% 1/1,456,966 alleles · very rare

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: ACO2
Protein: p.Gln780fs
Coding: c.2338_2339del
MANE Select: NM_001018050 · reported on NM_001098
dbSNP: rs1114167284
Type: Deletion
Location: chr22:41528607 (GRCh38)

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

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-gln780fs (accessed [today's date]).

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