Is ACAD9 p.Ala190Val (c.569C>T) pathogenic?

ACAD9 p.Ala190Val (c.569C>T) is classified Uncertain significance in ACAD9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-15). AlphaMissense: likely benign (0.2751); Very rare (popmax 0.000509%, nfe).

How common is ACAD9 p.Ala190Val (c.569C>T) in the general population?

ACAD9 p.Ala190Val (c.569C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about ACAD9 p.Ala190Val (c.569C>T)?

AlphaMissense predicts likely benign (score 0.2751) — an in-silico prediction, not a clinical call.

ACAD9 p.Ala190Val

c.569C>T · rs548599849 · VCV425309

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2751	likely benign
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -4.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.36 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,808 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,604 alleles · very rare

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.Ala190Val
Coding: c.569C>T
MANE Select: NM_014049
dbSNP: rs548599849
Type: single nucleotide variant
Location: chr3:128897646 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 2 PDB
Residue 190: a β-strand

Full ACAD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD9 p.Ala190= 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
ACAD9 c.1358+2T>G Likely pathogenic ★★ same type
ACAD9 c.1359-1G>A Pathogenic/Likely pathogenic ★★ same type
ACAD9 c.1563+1G>A Pathogenic/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-ala190val (accessed [today's date]).

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