Is ACADS p.Ala302Val (c.905C>T) pathogenic?

ACADS p.Ala302Val (c.905C>T) is classified Conflicting classifications of pathogenicity in ACADS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-08-14). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.00492%, nfe); Associated with short chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADS p.Ala302Val (c.905C>T)?

ACADS p.Ala302Val (c.905C>T) is associated with short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ala302Val (c.905C>T) in the general population?

ACADS p.Ala302Val (c.905C>T) is very rare (popmax 0.00492%, 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.

What do computational predictors say about ACADS p.Ala302Val (c.905C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

ACADS p.Ala302Val

c.905C>T · rs770009021 · VCV1125581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

short chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -3.4, phastCons 0.09
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	14.41	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 58/1,180,028 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00428% 69/1,612,550 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,345
East Asian	0.00445%	22,448
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,237
African / African-American	0.00267%	37,465
Admixed American	0.00167%	60,014
Finnishnot grpmax-eligible	0.0016%	62,518

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.Ala302Val
Coding: c.905C>T
MANE Select: NM_000017
dbSNP: rs770009021
Type: single nucleotide variant
Location: chr12:120738642 (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.Ala302= Conflicting classifications of pathogenicity ★ same residue
ACADS p.Ala302Glu Uncertain significance ★ ⚠ 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

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-ala302val (accessed [today's date]).

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