Is ACAD9 p.Ser395fs (c.1185_1188del) pathogenic?

ACAD9 p.Ser395fs (c.11851188del) is classified Pathogenic in ACAD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). Very rare (popmax 8.47e-05%, nfe); Associated with acyl-CoA dehydrogenase 9 deficiency.

What condition is associated with ACAD9 p.Ser395fs (c.1185_1188del)?

ACAD9 p.Ser395fs (c.1185_1188del) is associated with acyl-CoA dehydrogenase 9 deficiency (ClinVar).

How common is ACAD9 p.Ser395fs (c.1185_1188del) in the general population?

ACAD9 p.Ser395fs (c.1185_1188del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Acyl-CoA dehydrogenase 9 deficiency inherited?

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

ACAD9 p.Ser395fs

c.1185_1188del · rs2529272954 · VCV2500742

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

acyl-CoA dehydrogenase 9 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 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.2	GERP -2.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,864 alleles · very rare

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: ACAD9
Protein: p.Ser395fs
Coding: c.1185_1188del
MANE Select: NM_014049
dbSNP: rs2529272954
Type: Microsatellite
Location: chr3:128906151 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB
Residue 395: an α-helix

Full ACAD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acyl-CoA dehydrogenase 9 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acyl-CoA dehydrogenase 9 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ACAD9 c.153_156del Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Gln585fs Likely pathogenic ★★ same condition
ACAD9 p.Ile431fs Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Thr462fs Pathogenic/Likely pathogenic ★★ same condition
ACAD9 c.808+63GT[14] Benign ★★ same condition
ACAD9 c.-65GT[4] Benign ★★ same condition
ACAD9 p.Ser602fs Likely pathogenic ★ same condition
ACAD9 c.1150-2A>G 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/acad9-p-ser395fs (accessed [today's date]).

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