Is ACADS p.Ala172= (c.516C>T) pathogenic?

ACADS p.Ala172= (c.516C>T) is classified Conflicting classifications of pathogenicity in ACADS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-09). Rare (popmax 0.305%, sas); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Ala172= (c.516C>T)?

ACADS p.Ala172= (c.516C>T) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ala172= (c.516C>T) in the general population?

ACADS p.Ala172= (c.516C>T) is rare (popmax 0.305%, sas) (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.Ala172=

c.516C>T · rs531683812 · VCV880759

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.305%, sas)

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2	GERP -4
Overall
CADD	0.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.305% South Asian · 278/91,078 alleles

Filtering AF 0.276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.264%

Overall 0.0183% 296/1,614,018 alleles · rare exomes 285/1,461,798 · genomes 11/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.305%	328
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0096%	10,416
East Asian	0.00668%	14,960
European (non-Finnish)	0.000678%	147,495

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.Ala172=
Coding: c.516C>T
MANE Select: NM_000017
dbSNP: rs531683812
Type: single nucleotide variant
Location: chr12:120737880 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 172: 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.Ala172fs Pathogenic ★ 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-ala172 (accessed [today's date]).

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