Is ACADVL p.Ser92= (c.276C>T) pathogenic?

ACADVL p.Ser92= (c.276C>T) is classified Conflicting classifications of pathogenicity in ACADVL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0366%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACADVL p.Ser92= (c.276C>T)?

ACADVL p.Ser92= (c.276C>T) is associated with Inborn genetic diseases, very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Ser92= (c.276C>T) in the general population?

ACADVL p.Ser92= (c.276C>T) is ultra-rare (popmax 0.0366%, amr) (gnomAD).

ACADVL p.Ser92=

c.276C>T · rs530278910 · VCV1462063

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0366%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -4.2
Overall
CADD	1.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0366% Admixed American · 22/60,030 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00149% 24/1,614,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0366%	2,729
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Ser92=
Coding: c.276C>T
MANE Select: NM_000018
dbSNP: rs530278910
Type: single nucleotide variant
Location: chr17:7220675 (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 92: the 'catalytic' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: very long chain acyl-CoA dehydrogenase deficiency

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-ser92 (accessed [today's date]).

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