Is ACADS p.Ala165fs (c.492_513del) pathogenic?

ACADS p.Ala165fs (c.492513del) is classified Pathogenic/Likely pathogenic in ACADS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-18). Very rare (popmax 0.00333%, amr); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Ala165fs (c.492_513del)?

ACADS p.Ala165fs (c.492_513del) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ala165fs (c.492_513del) in the general population?

ACADS p.Ala165fs (c.492_513del) is very rare (popmax 0.00333%, amr) (gnomAD).

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.Ala165fs

c.492_513del · rs745833347 · VCV953991

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -14	GERP -4.3
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00136% 22/1,613,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
European (non-Finnish)	0.00161%	62,101
African / African-American	0.00134%	74,860

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.Ala165fs
Coding: c.492_513del
MANE Select: NM_000017
dbSNP: rs745833347
Type: Deletion
Location: chr12:120737854 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 165: 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.Ala165Val Uncertain significance ★ ⚠ same residue
ACADS p.Glu228fs Pathogenic ★★ same condition
ACADS p.Ala315del Uncertain significance ★★ same condition
ACADS p.Lys51del Uncertain significance ★★ same condition
ACADS p.Ala378fs Likely pathogenic ★ same condition
ACADS p.Asn188fs Pathogenic ★ same condition
ACADS p.Glu389fs Pathogenic ★ same condition
ACADS p.Gly11fs 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-ala165fs (accessed [today's date]).

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