ACACA p.Gln1656=
c.4968A>G · rs146371757 · VCV1989058
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.297%, mid)
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 0.7 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 3.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.297%
Middle Eastern · 18/6,058 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.0147%
238/1,614,152 alleles · rare
exomes 192/1,461,850 · genomes 46/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.297% | 337 |
| Amishnot grpmax-eligible | 0.11% | 910 |
| Admixed American | 0.0716% | 1,396 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0236% | 4,229 |
| South Asian | 0.0198% | 5,060 |
| European (non-Finnish) | 0.011% | 9,077 |
| African / African-American | 0.00533% | 18,761 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
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.Gln1656=
- Coding
- c.4968A>G
- MANE Select
- NM_198834
- dbSNP
- rs146371757
- Type
- single nucleotide variant
- Location
- chr17:37179371 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.05 · 10 PDB
- Residue 1656
- a β-strand; the coa carboxyltransferase n-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-gln1656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown