Is ACADS p.Arg20Lys (c.59G>A) pathogenic?

ACADS p.Arg20Lys (c.59G>A) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-26). AlphaMissense: likely benign (0.1188); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACADS p.Arg20Lys (c.59G>A)?

ACADS p.Arg20Lys (c.59G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACADS p.Arg20Lys (c.59G>A) in the general population?

ACADS p.Arg20Lys (c.59G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ACADS p.Arg20Lys (c.59G>A)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

ACADS p.Arg20Lys

c.59G>A · rs139981498 · VCV2239254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -8.94	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 0.018	GERP -2.6
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	6.26	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 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,194 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.Arg20Lys
Coding: c.59G>A
MANE Select: NM_000017
dbSNP: rs139981498
Type: single nucleotide variant
Location: chr12:120727038 (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

Disease context

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

Similar variants

ACADS p.Arg20Gly Uncertain significance ★ ⚠ same residue
ACADS p.Arg330Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACADS p.Gly209Ser Benign/Likely benign ★★ same condition
ACADS p.Ala385Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
ACADS p.Ala166= Likely benign ★ same condition
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

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-arg20lys (accessed [today's date]).

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