Is ACO2 p.Gln434Ter (c.1300C>T) pathogenic?

ACO2 p.Gln434Ter (c.1300C>T) is classified Pathogenic in ACO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). Very rare (popmax 6.85e-05%); Associated with inherited retinal dystrophy.

What condition is associated with ACO2 p.Gln434Ter (c.1300C>T)?

ACO2 p.Gln434Ter (c.1300C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is ACO2 p.Gln434Ter (c.1300C>T) in the general population?

ACO2 p.Gln434Ter (c.1300C>T) is very rare (popmax 6.85e-05%) (gnomAD).

ACO2 p.Gln434Ter

c.1300C>T · VCV3249330

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Conditions

inherited retinal dystrophy

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 in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 18
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.61, phastCons 0.78
Overall
CADD	35.0	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 6.85e-05%

Overall 6.85e-05% 1/1,459,386 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.Gln434Ter
Coding: c.1300C>T
MANE Select: NM_001098
Type: single nucleotide variant
Location: chr22:41523208 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACO2 p.Gly240Ala Uncertain significance ★★ ⚠ same condition
ACO2 p.Thr761Met Uncertain significance ★★ ⚠ same condition
ACO2 p.Val247Ala Uncertain significance ★★ ⚠ same condition
ACO2 p.Leu74Val Conflicting classifications of pathogenicity ★ ⚠ same condition
ACO2 p.Lys258Asn Uncertain significance ★ ⚠ same condition
ACO2 c.1483-5T>G Uncertain significance same condition
ACO2 p.Arg378Ter Pathogenic/Likely pathogenic ★★ same type
ACO2 p.Arg58Ter Pathogenic/Likely pathogenic ★★ same type

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-gln434ter (accessed [today's date]).

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