Is ACADS p.Cys109Arg (c.325T>C) pathogenic?

ACADS p.Cys109Arg (c.325T>C) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-16). AlphaMissense: likely pathogenic (0.9842); Absent from gnomAD v4.1.

How common is ACADS p.Cys109Arg (c.325T>C) in the general population?

ACADS p.Cys109Arg (c.325T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADS p.Cys109Arg (c.325T>C)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

ACADS p.Cys109Arg

c.325T>C · VCV3380123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic · top 6% in ACADS
REVEL	0.968	strongly pathogenic-leaning
SaProt	LLR -15.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ACADS
Protein: p.Cys109Arg
Coding: c.325T>C
MANE Select: NM_000017
Type: single nucleotide variant
Location: chr12:120737100 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB

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

Similar variants

ACADS p.Cys109= Conflicting classifications of pathogenicity ★ same residue
ACADS p.Cys109_Ala110delinsSer Conflicting classifications of pathogenicity ★ same residue
ACADS c.211-2A>G Likely pathogenic ★★ same type
ACADS c.625-1G>A Likely pathogenic ★★ same type
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same type
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same type
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same type
ACADS p.Arg272Cys 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/acads-p-cys109arg (accessed [today's date]).

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