ACACA p.Arg2148=
c.6444A>C · rs55811414 · VCV559340
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 10.4%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.43 | GERP -2.7, phastCons 0.15 |
| Overall | ||
| CADD | 6.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.4%
African / African-American · 7,803/74,986 alleles
Filtering AF
10.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.1%
Overall
0.85%
13,724/1,614,092 alleles · common
exomes 8,543/1,461,864 · genomes 5,181/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.4% | 10 |
| Ashkenazi Jewishnot grpmax-eligible | 3.83% | 26 |
| Admixed American | 1.79% | 56 |
| Middle Eastern | 1.65% | 61 |
| Remaining individualsnot grpmax-eligible | 1.52% | 66 |
| Amishnot grpmax-eligible | 0.987% | 101 |
| European (non-Finnish) | 0.222% | 451 |
| South Asian | 0.0461% | 2,168 |
| Finnishnot grpmax-eligible | 0.00312% | 32,015 |
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.Arg2148=
- Coding
- c.6444A>C
- MANE Select
- NM_198834
- dbSNP
- rs55811414
- Type
- single nucleotide variant
- Location
- chr17:37113096 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 10 PDB
- Residue 2148
- an α-helix; the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region
Similar variants
- ACACA p.Arg2148Ter Uncertain significance ★ same residue
- 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
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-arg2148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown