Is ACADS p.Arg23Gln (c.68G>A) pathogenic?

ACADS p.Arg23Gln (c.68G>A) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0999); Very rare (popmax 0.00267%, afr); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Arg23Gln (c.68G>A)?

ACADS p.Arg23Gln (c.68G>A) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Arg23Gln (c.68G>A) in the general population?

ACADS p.Arg23Gln (c.68G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ACADS p.Arg23Gln (c.68G>A)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

ACADS p.Arg23Gln

c.68G>A · rs773600043 · VCV1021442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 1.7, phastCons 0.94
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,870 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00112% 18/1,613,922 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-Americangrpmax	0.00267%	37,435
Remaining individualsnot grpmax-eligible	0.0016%	62,490
Finnishnot grpmax-eligible	0.00156%	63,988
South Asian	0.0011%	91,070
European (non-Finnish)	0.00102%	98,334

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Protein: p.Arg23Gln
Coding: c.68G>A
MANE Select: NM_000017
dbSNP: rs773600043
Type: single nucleotide variant
Location: chr12:120727047 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB

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

Disease context

short chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Short chain acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ACADS p.Arg23Pro Uncertain significance ★ ⚠ same residue
ACADS p.Arg23Trp Uncertain significance ★ ⚠ same residue
ACADS p.Arg23= Likely benign ★ same residue
ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A Likely pathogenic ★★ same condition
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same condition

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-p-arg23gln (accessed [today's date]).

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