Is ACADS p.Ala385Ser (c.1153G>T) pathogenic?

ACADS p.Ala385Ser (c.1153G>T) is classified Conflicting classifications of pathogenicity in ACADS (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-05-23). AlphaMissense: likely benign (0.1525); Ultra-rare (popmax 0.06%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACADS p.Ala385Ser (c.1153G>T)?

ACADS p.Ala385Ser (c.1153G>T) is associated with Inborn genetic diseases, short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ala385Ser (c.1153G>T) in the general population?

ACADS p.Ala385Ser (c.1153G>T) is ultra-rare (popmax 0.06%, amr) (gnomAD).

What do computational predictors say about ACADS p.Ala385Ser (c.1153G>T)?

AlphaMissense predicts likely benign (score 0.1525) — an in-silico prediction, not a clinical call.

ACADS p.Ala385Ser

c.1153G>T · rs202124189 · VCV379779

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1525 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1525	likely benign
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -9.62	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	25.1	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 0.06% Admixed American · 36/60,022 alleles

Filtering AF 0.0444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00316% 51/1,613,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.06%	1,667
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.004%	25,021
European (non-Finnish)	0.000254%	393,321

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.Ala385Ser
Coding: c.1153G>T
MANE Select: NM_000017
dbSNP: rs202124189
Type: single nucleotide variant
Location: chr12:120739362 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 385: 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.Ala385Thr 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
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg325Gln Pathogenic/Likely 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-ala385ser (accessed [today's date]).

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