Is ACADS p.Gln206Pro (c.617A>C) pathogenic?

ACADS p.Gln206Pro (c.617A>C) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1577); Very rare (popmax 8.47e-05%, nfe); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Gln206Pro (c.617A>C)?

ACADS p.Gln206Pro (c.617A>C) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Gln206Pro (c.617A>C) in the general population?

ACADS p.Gln206Pro (c.617A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

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

What do computational predictors say about ACADS p.Gln206Pro (c.617A>C)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

ACADS p.Gln206Pro

c.617A>C · VCV3611186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -8.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1, phastCons 0.44
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	22.0	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 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.84e-05% 1/1,461,618 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: ACADS
Protein: p.Gln206Pro
Coding: c.617A>C
MANE Select: NM_000017
Type: single nucleotide variant
Location: chr12:120737981 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 206: a turn

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

Disease context

short chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Short chain acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A Likely pathogenic ★★ same condition
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same condition
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg325Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg325Trp 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/acads-p-gln206pro (accessed [today's date]).

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