Is ACAD9 p.Ser602Phe (c.1805C>T) pathogenic?

ACAD9 p.Ser602Phe (c.1805C>T) is classified Likely pathogenic in ACAD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: likely pathogenic (0.744); Absent from gnomAD v4.1; Associated with mitochondrial complex I deficiency.

What condition is associated with ACAD9 p.Ser602Phe (c.1805C>T)?

ACAD9 p.Ser602Phe (c.1805C>T) is associated with mitochondrial complex I deficiency (ClinVar).

How common is ACAD9 p.Ser602Phe (c.1805C>T) in the general population?

ACAD9 p.Ser602Phe (c.1805C>T) is absent from gnomAD v4.1 (gnomAD).

How is Isolated complex I deficiency inherited?

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

What do computational predictors say about ACAD9 p.Ser602Phe (c.1805C>T)?

AlphaMissense predicts likely pathogenic (score 0.744) — an in-silico prediction, not a clinical call.

ACAD9 p.Ser602Phe

c.1805C>T · rs2529107329 · VCV2577092

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mitochondrial complex I deficiency

Computational evidence

Protein change
AlphaMissense	0.744	likely pathogenic ✓ concordant with ClinVar
REVEL	0.611	indeterminate
SaProt	LLR -13.33	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.55, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.36 · regional, not allelic
Overall
CADD	24.9	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.Ser602Phe
Coding: c.1805C>T
MANE Select: NM_014049
dbSNP: rs2529107329
Type: single nucleotide variant
Location: chr3:128912546 (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

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

For Isolated complex I deficiency (Orphanet):

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

Similar variants

ACAD9 p.Ser602= Uncertain significance same residue
ACAD9 c.634-1G>A Likely pathogenic ★★ same condition
ACAD9 p.Ala326Pro Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Arg266Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACAD9 p.Arg414Ser Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Arg417Cys Pathogenic/Likely pathogenic ★★ same condition
ACAD9 p.Arg518Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACAD9 p.Arg532Trp 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-ser602phe (accessed [today's date]).

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