Is ACADS p.Thr37fs (c.107dup) pathogenic?

ACADS p.Thr37fs (c.107dup) is classified Conflicting classifications of pathogenicity in ACADS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-11-07). Very rare (popmax 0.01%, amr); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Thr37fs (c.107dup)?

ACADS p.Thr37fs (c.107dup) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Thr37fs (c.107dup) in the general population?

ACADS p.Thr37fs (c.107dup) is very rare (popmax 0.01%, amr) (gnomAD).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

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

ACADS p.Thr37fs

c.107dup · rs750941135 · VCV550479

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,008 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Thr37fs
Coding: c.107dup
MANE Select: NM_000017
dbSNP: rs750941135
Type: Duplication
Location: chr12:120727085 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 37: an α-helix

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 p.Leu304fs Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala172fs Pathogenic ★ same condition
ACADS p.Glu36fs Pathogenic ★ same condition
ACADS p.Pro19fs Likely pathogenic ★ same condition
ACADS c.1030-3_1044dup Uncertain significance ★ same condition
ACADS p.Ala13fs Likely pathogenic same condition
ACADS p.Lys226fs Likely pathogenic same condition
ACADS p.Met317_Ala318dup Uncertain significance 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-thr37fs (accessed [today's date]).

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