Is ACAD9 p.Pro55Leu (c.164C>T) pathogenic?

ACAD9 p.Pro55Leu (c.164C>T) is classified Uncertain significance in ACAD9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-20). AlphaMissense: ambiguous (0.3907); Absent from gnomAD v4.1; Associated with acyl-CoA dehydrogenase 9 deficiency.

What condition is associated with ACAD9 p.Pro55Leu (c.164C>T)?

ACAD9 p.Pro55Leu (c.164C>T) is associated with acyl-CoA dehydrogenase 9 deficiency (ClinVar).

How common is ACAD9 p.Pro55Leu (c.164C>T) in the general population?

ACAD9 p.Pro55Leu (c.164C>T) is absent from gnomAD v4.1 (gnomAD).

How is Acyl-CoA dehydrogenase 9 deficiency inherited?

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

What do computational predictors say about ACAD9 p.Pro55Leu (c.164C>T)?

AlphaMissense predicts ambiguous (score 0.3907) — an in-silico prediction, not a clinical call.

ACAD9 p.Pro55Leu

c.164C>T · VCV4063902

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

acyl-CoA dehydrogenase 9 deficiency

Computational evidence

Protein change
AlphaMissense	0.3907	ambiguous
REVEL	0.781	moderately pathogenic-leaning
SaProt	LLR -12.27	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Pangolin	Δ0.21	gain · loss 0.10 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.36 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACAD9
Protein: p.Pro55Leu
Coding: c.164C>T
MANE Select: NM_014049
Type: single nucleotide variant
Location: chr3:128884666 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB
Residue 55: a β-strand

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.Pro55= Likely benign ★ 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
ACAD9 c.1A>G 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-pro55leu (accessed [today's date]).

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