ACACA p.Leu2212=
c.6634C>T · rs148586245 · VCV1600886
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.236%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 9.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.236%
European (non-Finnish) · 2,783/1,180,030 alleles
Filtering AF
0.229%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.225%
Overall
0.179%
2,888/1,614,154 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.236% | 424 |
| Remaining individualsnot grpmax-eligible | 0.08% | 1,250 |
| African / African-American | 0.0466% | 2,144 |
| Finnishnot grpmax-eligible | 0.0203% | 4,926 |
| Admixed American | 0.0117% | 8,572 |
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
- ACACA
- Protein
- p.Leu2212=
- Coding
- c.6634C>T
- MANE Select
- NM_198834
- dbSNP
- rs148586245
- Type
- single nucleotide variant
- Location
- chr17:37097916 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 10 PDB
- Residue 2212
- an α-helix; the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region
Similar variants
- ACACA p.Ala2308Val Uncertain significance ★★ ⚠ same type
- ACACA p.Arg1206His Uncertain significance ★★ ⚠ same type
- ACACA p.Arg2198Gln Uncertain significance ★★ ⚠ same type
- ACACA p.Arg745Trp Uncertain significance ★★ ⚠ same type
- ACACA p.Asn1903Ser Uncertain significance ★★ ⚠ same type
- ACACA p.Asn728Ser Uncertain significance ★★ ⚠ same type
- ACACA p.Asn950Ser Uncertain significance ★★ ⚠ same type
- ACACA p.Asp2228Asn Uncertain significance ★★ ⚠ 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/acaca-p-leu2212 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown