Is ACADVL p.Phe282Ser (c.845T>C) pathogenic?

ACADVL p.Phe282Ser (c.845T>C) is classified Conflicting classifications of pathogenicity in ACADVL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely pathogenic (0.9974); Absent from gnomAD v4.1; Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Phe282Ser (c.845T>C)?

ACADVL p.Phe282Ser (c.845T>C) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Phe282Ser (c.845T>C) in the general population?

ACADVL p.Phe282Ser (c.845T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADVL p.Phe282Ser (c.845T>C)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

ACADVL p.Phe282Ser

Q: How is Very long chain acyl-CoA dehydrogenase deficiency inherited?

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

c.845T>C · rs2071268683 · VCV1019298

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

very long chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic · top 1% in ACADVL
REVEL	0.981	strongly pathogenic-leaning
SaProt	LLR -15.57	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	29.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACADVL
Protein: p.Phe282Ser
Coding: c.845T>C
MANE Select: NM_000018
dbSNP: rs2071268683
Type: single nucleotide variant
Location: chr17:7222269 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.65 · 3 PDB
Residue 282: a β-strand; the 'catalytic' region

Full ACADVL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

very long chain acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Very long chain acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ACADVL c.1077+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1077+1G>T Likely pathogenic ★★★ same condition
ACADVL c.1077+2T>A Pathogenic ★★★ same condition
ACADVL c.1077+2T>C Pathogenic ★★★ same condition
ACADVL c.1182+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1269+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1532+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1532+2T>C 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/acadvl-p-phe282ser (accessed [today's date]).

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