Is ACAD9 p.Ser2Arg (c.6C>G) pathogenic?

ACAD9 p.Ser2Arg (c.6C>G) is classified Uncertain significance in ACAD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.1441); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACAD9 p.Ser2Arg (c.6C>G)?

ACAD9 p.Ser2Arg (c.6C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACAD9 p.Ser2Arg (c.6C>G) in the general population?

ACAD9 p.Ser2Arg (c.6C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAD9 p.Ser2Arg (c.6C>G)?

AlphaMissense predicts likely benign (score 0.1441) — an in-silico prediction, not a clinical call.

ACAD9 p.Ser2Arg

c.6C>G · rs766980679 · VCV2295928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1441 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1441	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -3.4
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.36 · regional, not allelic
Overall
CADD	11.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser2Arg
Coding: c.6C>G
MANE Select: NM_014049
dbSNP: rs766980679
Type: single nucleotide variant
Location: chr3:128879697 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACAD9 p.Ser2Asn Uncertain significance ★ ⚠ same residue
ACAD9 p.Ser2Gly Uncertain significance ★ ⚠ same residue
ACAD9 p.Ser2Ile Uncertain significance ★ ⚠ same residue
ACAD9 p.Ser2= Likely benign ★ same residue
ACAD9 c.1149+5C>A Uncertain significance ★★ same condition
ACAD9 p.Ala397Val Uncertain significance ★★ ⚠ same condition
ACAD9 p.Ala495= Uncertain significance ★★ same condition
ACAD9 p.Ala495Val Uncertain significance ★★ ⚠ 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-ser2arg (accessed [today's date]).

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