Is ACADS p.Arg330= (c.990C>T) pathogenic?

ACADS p.Arg330= (c.990C>T) is classified Benign in ACADS (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 89.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Arg330= (c.990C>T)?

ACADS p.Arg330= (c.990C>T) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

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

ACADS p.Arg330=

Q: How common is ACADS p.Arg330= (c.990C>T) in the general population?

ACADS p.Arg330= (c.990C>T) is common (popmax 89.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.990C>T · rs3915 · VCV136260

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 89.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

short chain acyl-CoA dehydrogenase 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 -20	GERP -3.9
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 89.5% African / African-American · 67,128/75,034 alleles

Filtering AF 88.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 88.7%

Overall 48.5% 782,575/1,613,652 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	89.5%	1
South Asian	64.6%	2
Middle Eastern	62.9%	2
Admixed American	62%	2
Remaining individualsnot grpmax-eligible	51.2%	2
East Asian	49.2%	2
Ashkenazi Jewishnot grpmax-eligible	48.3%	2
Finnishnot grpmax-eligible	45.2%	2
European (non-Finnish)	43.9%	2
Amishnot grpmax-eligible	43.9%	2

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.Arg330=
Coding: c.990C>T
MANE Select: NM_000017
dbSNP: rs3915
Type: single nucleotide variant
Location: chr12:120738876 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 330: an α-helix

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.Arg330Cys Pathogenic/Likely pathogenic ★★ ⚠ same residue
ACADS p.Arg330His Pathogenic/Likely pathogenic ★★ same residue
ACADS p.Arg330Leu Uncertain significance ★ 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-arg330 (accessed [today's date]).

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