Is ACADVL p.Ala577Thr (c.1729G>A) pathogenic?

ACADVL p.Ala577Thr (c.1729G>A) is classified Uncertain significance in ACADVL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1252); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACADVL p.Ala577Thr (c.1729G>A)?

ACADVL p.Ala577Thr (c.1729G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACADVL p.Ala577Thr (c.1729G>A) in the general population?

ACADVL p.Ala577Thr (c.1729G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADVL p.Ala577Thr (c.1729G>A)?

AlphaMissense predicts likely benign (score 0.1252) — an in-silico prediction, not a clinical call.

ACADVL p.Ala577Thr

c.1729G>A · VCV4565051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1252 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1252	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -0.11, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ala577Thr
Coding: c.1729G>A
MANE Select: NM_000018
Type: single nucleotide variant
Location: chr17:7224692 (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 577: an α-helix

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

Similar variants

ACADVL p.Ala577fs Likely pathogenic ★★★ same residue
ACADVL p.Ala415Val Pathogenic/Likely pathogenic ★★ same condition
ACADVL c.139-3C>T Uncertain significance ★★ same condition
ACADVL p.Ala124Ser Uncertain significance ★★ ⚠ same condition
ACADVL p.Ala274Val Uncertain significance ★★ ⚠ same condition
ACADVL p.Ala36Val Uncertain significance ★★ ⚠ same condition
ACADVL p.Ala384Pro Uncertain significance ★★ ⚠ same condition
ACADVL p.Ala48Thr Uncertain significance ★★ ⚠ 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-ala577thr (accessed [today's date]).

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