Is ACADVL p.Pro219Ser (c.655C>T) pathogenic?

ACADVL p.Pro219Ser (c.655C>T) is classified Likely pathogenic in ACADVL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). AlphaMissense: likely benign (0.2469); Absent from gnomAD v4.1; Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Pro219Ser (c.655C>T)?

ACADVL p.Pro219Ser (c.655C>T) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Pro219Ser (c.655C>T) in the general population?

ACADVL p.Pro219Ser (c.655C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADVL p.Pro219Ser (c.655C>T)?

AlphaMissense predicts likely benign (score 0.2469) — an in-silico prediction, not a clinical call.

ACADVL p.Pro219Ser

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.655C>T · rs772898391 · VCV2759049

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2469 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

very long chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.2469	likely benign ⚠ discordant with ClinVar
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.34	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.95, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	21.5	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.Pro219Ser
Coding: c.655C>T
MANE Select: NM_000018
dbSNP: rs772898391
Type: single nucleotide variant
Location: chr17:7221984 (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 219: the 'catalytic' region; a binding site

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.Pro219His Likely pathogenic ★ ⚠ same residue
ACADVL p.Pro219Leu Likely pathogenic ★ ⚠ same residue
ACADVL p.Pro219Thr Pathogenic ★ ⚠ same residue
ACADVL p.Pro219= Uncertain significance 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

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-pro219ser (accessed [today's date]).

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