ACADS c.472+4C>A
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000679%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.35 | GERP -2.1, phastCons 0.29 |
| Overall | ||
| CADD | 16.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000679%
European (non-Finnish) · 8/1,177,408 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000548%
8/1,458,714 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
- ACADS
- Coding
- c.472+4C>A
- MANE Select
- NM_000017
- Type
- single nucleotide variant
- Location
- chr12:120737471 (GRCh38)
- Gene constraint
- LOEUF 0.852 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.58 · 4 PDB
Similar variants
- ACADS c.211-2A>G Likely pathogenic ★★ same type
- ACADS c.625-1G>A Likely pathogenic ★★ same type
- ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same type
- ACADS p.Arg107Cys Pathogenic ★★ ⚠ same type
- ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same type
- ACADS p.Arg325Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- ACADS p.Arg325Trp 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/acads-c-472-plus-4c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown