Is ACADSB p.Arg13Ser (c.39G>C) pathogenic?

ACADSB p.Arg13Ser (c.39G>C) is classified Uncertain significance in ACADSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.1213); Very rare (popmax 0.00497%, nfe).

How common is ACADSB p.Arg13Ser (c.39G>C) in the general population?

ACADSB p.Arg13Ser (c.39G>C) is very rare (popmax 0.00497%, nfe) (gnomAD).

What do computational predictors say about ACADSB p.Arg13Ser (c.39G>C)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

ACADSB p.Arg13Ser

c.39G>C · rs901402559 · VCV3251633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00497%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -5.29	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 0.72	GERP -4, phastCons 0.41
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.39 · regional, not allelic
Overall
CADD	10.39	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 0.00497% European (non-Finnish) · 57/1,146,712 alleles

Filtering AF 0.00388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00355%

Overall 0.00375% 58/1,546,206 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00497%	20,118
Admixed American	0.00196%	50,970

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: ACADSB
Protein: p.Arg13Ser
Coding: c.39G>C
MANE Select: NM_001609
dbSNP: rs901402559
Type: single nucleotide variant
Location: chr10:123009068 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.47 · 1 PDB
Residue 13: a UniProt-annotated variant site (in)

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

Similar variants

ACADSB p.Arg13Lys Benign ★★ same residue
ACADSB c.1128+1G>A Likely pathogenic ★★ same type
ACADSB c.1228+1G>A Likely pathogenic ★★ same type
ACADSB c.303+3A>G Pathogenic/Likely pathogenic ★★ same type
ACADSB p.Cys308Tyr Pathogenic/Likely pathogenic ★★ same type
ACADSB p.Gln99Ter Pathogenic/Likely pathogenic ★★ same type
ACADSB p.Glu387Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
ACADSB p.Gly410Ser 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/acadsb-p-arg13ser (accessed [today's date]).

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