Is ACAD9 p.Ser602= (c.1806C>T) pathogenic?

ACAD9 p.Ser602= (c.1806C>T) is classified Uncertain significance in ACAD9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-28). Very rare (popmax 0.000254%, nfe); Associated with acyl-CoA dehydrogenase 9 deficiency.

What condition is associated with ACAD9 p.Ser602= (c.1806C>T)?

ACAD9 p.Ser602= (c.1806C>T) is associated with acyl-CoA dehydrogenase 9 deficiency (ClinVar).

How common is ACAD9 p.Ser602= (c.1806C>T) in the general population?

ACAD9 p.Ser602= (c.1806C>T) is very rare (popmax 0.000254%, 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.Ser602=

c.1806C>T · VCV4063967

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

acyl-CoA dehydrogenase 9 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.378	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.1
Overall
CADD	7.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,030 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,014 alleles · very rare exomes 2/1,461,874 · genomes 1/152,140 · joint denominator

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.Ser602=
Coding: c.1806C>T
MANE Select: NM_014049
Type: single nucleotide variant
Location: chr3:128912547 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB
Residue 602: 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 p.Ser602fs Likely pathogenic ★ same residue
ACAD9 p.Ser602Phe Likely pathogenic ★ same residue
ACAD9 c.1150-2A>G Likely pathogenic ★★ same condition
ACAD9 c.1278+1G>T Likely pathogenic ★★ same condition
ACAD9 c.1279-2A>C Likely pathogenic ★★ same condition
ACAD9 c.1358+2T>G Likely pathogenic ★★ same condition
ACAD9 c.1359-1G>A Pathogenic/Likely pathogenic ★★ same condition
ACAD9 c.1563+1G>A 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/acad9-p-ser602 (accessed [today's date]).

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