ACO2 p.Trp455Ter
c.1364G>A · VCV4823908
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
optic atrophy 9
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 | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 43.0 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACO2
- Protein
- p.Trp455Ter
- Coding
- c.1364G>A
- MANE Select
- NM_001098
- Type
- single nucleotide variant
- Location
- chr22:41523272 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 p.Gly503Ter Pathogenic ★★ same condition
- ACO2 p.Arg684Gln Uncertain significance ★★ ⚠ same condition
- ACO2 p.Arg684Trp Uncertain significance ★★ ⚠ same condition
- ACO2 p.Glu321Lys Uncertain significance ★★ ⚠ same condition
- ACO2 p.Gly240Ala Uncertain significance ★★ ⚠ same condition
- ACO2 c.1032+17C>T Benign ★★ same condition
- ACO2 c.1370+48A>G Benign ★★ same condition
- ACO2 c.174-52G>T Benign ★★ 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-trp455ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown