ACO2 c.1605+5G>C
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.036%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +5 | donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.28 | donor loss · deltas |
| Pangolin | Δ0.80 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Non-coding constraint | Z 0.07 | 1 kb window · o/e 1.00 · regional · uncalibrated |
| Overall | ||
| CADD | 19.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.036%
African / African-American · 27/74,922 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0219%
Overall
0.00167%
27/1,614,040 alleles · ultra-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
- Coding
- c.1605+5G>C
- MANE Select
- NM_001098
- dbSNP
- rs746090988
- Type
- single nucleotide variant
- Location
- chr22:41524973 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 c.2208+5G>T Uncertain significance ★★ same condition
- ACO2 p.Ala500Thr Uncertain significance ★★ ⚠ same condition
- ACO2 p.Arg141His Uncertain significance ★★ ⚠ same condition
- ACO2 p.Arg18Gln Uncertain significance ★★ ⚠ same condition
- ACO2 p.Arg61Gln Uncertain significance ★★ ⚠ same condition
- ACO2 p.Arg633Leu Uncertain significance ★★ ⚠ same condition
- ACO2 p.Asp538Val Uncertain significance ★★ ⚠ same condition
- ACO2 p.Asp542Ala 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-c-1605-plus-5g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown