Is ACACA p.Gln641= (c.1923G>A) pathogenic?

ACACA p.Gln641= (c.1923G>A) is classified Benign in ACACA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 42.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with acetyl-coa carboxylase deficiency.

What condition is associated with ACACA p.Gln641= (c.1923G>A)?

ACACA p.Gln641= (c.1923G>A) is associated with acetyl-coa carboxylase deficiency (ClinVar).

ACACA p.Gln641=

Q: How common is ACACA p.Gln641= (c.1923G>A) in the general population?

ACACA p.Gln641= (c.1923G>A) is common (popmax 42.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1923G>A · rs2229416 · VCV559346

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 42.3%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

acetyl-coa carboxylase deficiency

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 1.7	GERP -0.91, phastCons 0.94
Overall
CADD	8.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.3% East Asian · 18,993/44,854 alleles

Filtering AF 41.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.6%

Overall 14.5% 234,069/1,614,036 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	42.3%	2
South Asian	33.3%	3
Middle Eastern	19.8%	5
Finnishnot grpmax-eligible	18.3%	5
Remaining individualsnot grpmax-eligible	16.4%	6
Admixed American	14.7%	7
Ashkenazi Jewishnot grpmax-eligible	13%	8
European (non-Finnish)	12.4%	8
Amishnot grpmax-eligible	4.19%	24
African / African-American	3.61%	28

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.Gln641=
Coding: c.1923G>A
MANE Select: NM_198834
dbSNP: rs2229416
Type: single nucleotide variant
Location: chr17:37252940 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB
Residue 641: an α-helix

Full ACACA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acetyl-coa carboxylase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACACA p.Ala2308Val Uncertain significance ★★ ⚠ same condition
ACACA p.Arg2198Gln Uncertain significance ★★ ⚠ same condition
ACACA p.Ala1548Thr Uncertain significance ★ ⚠ same condition
ACACA p.Arg2198Trp Uncertain significance ★ ⚠ same condition
ACACA p.Ala1657Thr Pathogenic ⚠ same condition
ACACA p.Pro2214His Pathogenic/Likely pathogenic same condition
ACACA c.3474+2TA[14] Uncertain significance ★ same condition
ACACA p.Arg1206His 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-gln641 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown