Is ACADS p.Pro142fs (c.423_424del) pathogenic?

ACADS p.Pro142fs (c.423424del) is classified Likely pathogenic in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-21). No gnomAD frequency available for this variant; Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Pro142fs (c.423_424del)?

ACADS p.Pro142fs (c.423_424del) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Pro142fs (c.423_424del) in the general population?

ACADS p.Pro142fs (c.423_424del) is no gnomAD frequency available for this variant (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.Pro142fs

c.423_424del · rs2501191093 · VCV1723983

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -4, phastCons 0.64

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACADS
Protein: p.Pro142fs
Coding: c.423_424del
MANE Select: NM_000017
dbSNP: rs2501191093
Type: Deletion
Location: chr12:120737417 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 142: 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.Pro142Arg Uncertain significance ★★ ⚠ same residue
ACADS p.Ala165fs Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Glu228fs Pathogenic ★★ same condition
ACADS p.Ala315del Uncertain significance ★★ same condition
ACADS p.Lys51del Uncertain significance ★★ same condition
ACADS p.Ala378fs Likely pathogenic ★ same condition
ACADS p.Asn188fs Pathogenic ★ same condition
ACADS p.Glu389fs 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-pro142fs (accessed [today's date]).

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