Is ACADS p.Ser176Ter (c.527C>A) pathogenic?

ACADS p.Ser176Ter (c.527C>A) is classified Pathogenic in ACADS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-20). Very rare (popmax 0.000339%, nfe); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Ser176Ter (c.527C>A)?

ACADS p.Ser176Ter (c.527C>A) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ser176Ter (c.527C>A) in the general population?

ACADS p.Ser176Ter (c.527C>A) is very rare (popmax 0.000339%, nfe) (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.Ser176Ter

c.527C>A · rs1057516848 · VCV370891

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1, phastCons 1
Overall
CADD	36.0	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 0.000339% European (non-Finnish) · 4/1,179,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,836 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.Ser176Ter
Coding: c.527C>A
MANE Select: NM_000017
dbSNP: rs1057516848
Type: single nucleotide variant
Location: chr12:120737891 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 176: a β-strand

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.Ser176= Likely benign ★ same residue
ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A Likely pathogenic ★★ same condition
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala199Val Likely pathogenic ★★ same condition
ACADS p.Arg107Cys Pathogenic ★★ same condition
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg325Gln Pathogenic/Likely 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-ser176ter (accessed [today's date]).

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