Is ACADS p.Arg330Cys (c.988C>T) pathogenic?

ACADS p.Arg330Cys (c.988C>T) is classified Pathogenic/Likely pathogenic in ACADS (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-20). AlphaMissense: ambiguous (0.4676); Rare (popmax 0.135%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACADS p.Arg330Cys (c.988C>T)?

ACADS p.Arg330Cys (c.988C>T) is associated with Inborn genetic diseases, short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Arg330Cys (c.988C>T) in the general population?

ACADS p.Arg330Cys (c.988C>T) is rare (popmax 0.135%, afr) (gnomAD).

What do computational predictors say about ACADS p.Arg330Cys (c.988C>T)?

AlphaMissense predicts ambiguous (score 0.4676) — an in-silico prediction, not a clinical call.

ACADS p.Arg330Cys

c.988C>T · rs140853839 · VCV203557

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

ambiguous

0.4676 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4676	ambiguous
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -13.11	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% African / African-American · 101/75,052 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.00874% 141/1,613,868 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.135%	743
Admixed American	0.0183%	5,458
Remaining individualsnot grpmax-eligible	0.0128%	7,813
South Asian	0.00549%	18,216
East Asian	0.00223%	44,876
Finnishnot grpmax-eligible	0.00157%	63,724
European (non-Finnish)	0.00119%	84,286

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.Arg330Cys
Coding: c.988C>T
MANE Select: NM_000017
dbSNP: rs140853839
Type: single nucleotide variant
Location: chr12:120738874 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: short chain acyl-CoA dehydrogenase deficiency

Similar variants

ACADS p.Arg330= Benign ★★ 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-arg330cys (accessed [today's date]).

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