Is ACAD9 p.Ser2Asn (c.5G>A) pathogenic?

ACAD9 p.Ser2Asn (c.5G>A) is classified Uncertain significance in ACAD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). AlphaMissense: likely benign (0.0907); Very rare (popmax 0.00133%, afr).

How common is ACAD9 p.Ser2Asn (c.5G>A) in the general population?

ACAD9 p.Ser2Asn (c.5G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ACAD9 p.Ser2Asn (c.5G>A)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

ACAD9 p.Ser2Asn

c.5G>A · rs761385146 · VCV2417623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.4
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.36 · regional, not allelic
Overall
CADD	0.959	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

Grpmax group 0.00133% African / African-American · 1/75,010 alleles

Overall 0.000137% 2/1,460,036 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,010
European (non-Finnish)	8.48e-05%	1,179,894

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.Ser2Asn
Coding: c.5G>A
MANE Select: NM_014049
dbSNP: rs761385146
Type: single nucleotide variant
Location: chr3:128879696 (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

Similar variants

ACAD9 p.Ser2Arg 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.1030-1G>A Pathogenic/Likely pathogenic ★★ same type
ACAD9 c.1150-2A>G Likely pathogenic ★★ same type
ACAD9 c.1278+1G>T Likely pathogenic ★★ same type
ACAD9 c.1279-2A>C Likely pathogenic ★★ same type

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-ser2asn (accessed [today's date]).

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