Is ACADVL p.Ser489Arg (c.1467T>G) pathogenic?

ACADVL p.Ser489Arg (c.1467T>G) is classified Conflicting classifications of pathogenicity in ACADVL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-14). AlphaMissense: likely benign (0.1709); Absent from gnomAD v4.1; Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Ser489Arg (c.1467T>G)?

ACADVL p.Ser489Arg (c.1467T>G) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Ser489Arg (c.1467T>G) in the general population?

ACADVL p.Ser489Arg (c.1467T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADVL p.Ser489Arg (c.1467T>G)?

AlphaMissense predicts likely benign (score 0.1709) — an in-silico prediction, not a clinical call.

ACADVL p.Ser489Arg

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.1467T>G · rs771117714 · VCV932810

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1709 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

very long chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.1709	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -5.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	acceptor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.20	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.32	GERP -3, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	9.174	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.Ser489Arg
Coding: c.1467T>G
MANE Select: NM_000018
dbSNP: rs771117714
Type: single nucleotide variant
Location: chr17:7224178 (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 489: the 'membrane-anchoring' 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 p.Ser489= Likely benign ★ same residue
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

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-ser489arg (accessed [today's date]).

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