Is ACADVL p.Ser72Phe (c.215C>T) pathogenic?

ACADVL p.Ser72Phe (c.215C>T) is classified Conflicting classifications of pathogenicity in ACADVL (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.9733); Very rare (popmax 8.47e-05%, nfe); Associated with very long chain acyl-CoA dehydrogenase deficiency.

What condition is associated with ACADVL p.Ser72Phe (c.215C>T)?

ACADVL p.Ser72Phe (c.215C>T) is associated with very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Ser72Phe (c.215C>T) in the general population?

ACADVL p.Ser72Phe (c.215C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ACADVL p.Ser72Phe (c.215C>T)?

AlphaMissense predicts likely pathogenic (score 0.9733) — an in-silico prediction, not a clinical call.

ACADVL p.Ser72Phe

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.215C>T · rs1161495077 · VCV932742

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

very long chain acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9733	likely pathogenic · top 9% in ACADVL
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -10.35	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	30.0	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 0.000137% 2/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,030

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACADVL
Protein: p.Ser72Phe
Coding: c.215C>T
MANE Select: NM_000018
dbSNP: rs1161495077
Type: single nucleotide variant
Location: chr17:7220614 (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 72: 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 p.Ser72= 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-ser72phe (accessed [today's date]).

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