Is ACADS p.Ala81Val (c.242C>T) pathogenic?

ACADS p.Ala81Val (c.242C>T) is classified Uncertain significance in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.7467); Very rare (popmax 0.00134%, afr); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Ala81Val (c.242C>T)?

ACADS p.Ala81Val (c.242C>T) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ala81Val (c.242C>T) in the general population?

ACADS p.Ala81Val (c.242C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Short chain acyl-CoA dehydrogenase deficiency inherited?

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

What do computational predictors say about ACADS p.Ala81Val (c.242C>T)?

AlphaMissense predicts likely pathogenic (score 0.7467) — an in-silico prediction, not a clinical call.

ACADS p.Ala81Val

c.242C>T · rs1883464095 · VCV946300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.7467	likely pathogenic
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000621% 10/1,610,420 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
European (non-Finnish)	0.000763%	130,985

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.Ala81Val
Coding: c.242C>T
MANE Select: NM_000017
dbSNP: rs1883464095
Type: single nucleotide variant
Location: chr12:120737017 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB

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.Ala81= 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-ala81val (accessed [today's date]).

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