Is ACAD9 p.Phe120fs (c.359del) pathogenic?

ACAD9 p.Phe120fs (c.359del) is classified Pathogenic/Likely pathogenic in ACAD9 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-29). Rare (popmax 0.112%, amr); Associated with mitochondrial complex I deficiency.

What condition is associated with ACAD9 p.Phe120fs (c.359del)?

ACAD9 p.Phe120fs (c.359del) is associated with mitochondrial complex I deficiency, acyl-CoA dehydrogenase 9 deficiency (ClinVar).

How common is ACAD9 p.Phe120fs (c.359del) in the general population?

ACAD9 p.Phe120fs (c.359del) is rare (popmax 0.112%, amr) (gnomAD).

How is Isolated complex I deficiency inherited?

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

ACAD9 p.Phe120fs

c.359del · rs863224844 · VCV242524

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.112%, amr)

Conditions

mitochondrial complex I 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 4 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.8	GERP -1.8, phastCons 0.002
Overall
CADD	27.6	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 0.112% Admixed American · 67/59,802 alleles

Filtering AF 0.0905% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0826%

Overall 0.00819% 132/1,611,780 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.112%	893
Remaining individualsnot grpmax-eligible	0.016%	6,243
European (non-Finnish)	0.00458%	21,835
African / African-American	0.00134%	74,818

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.Phe120fs
Coding: c.359del
MANE Select: NM_014049
dbSNP: rs863224844
Type: Deletion
Location: chr3:128895321 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB

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

Disease context

mitochondrial complex I deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acyl-CoA dehydrogenase 9 deficiency

For Isolated complex I deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance, X-linked dominant
Onset: All ages

Similar variants

ACAD9 c.1359-45_1383del Likely pathogenic ★★ same condition
ACAD9 c.151-1_151del Pathogenic/Likely pathogenic ★★ same condition
ACAD9 c.1674_1692+34del Likely pathogenic ★★ same condition
ACAD9 p.Arg249fs Pathogenic ★★ same condition
ACAD9 p.Glu173fs Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Ile319fs Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Leu6fs Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Thr449fs 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-phe120fs (accessed [today's date]).

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