Is ACOX1 p.Val620Leu (c.1858G>T) pathogenic?

ACOX1 p.Val620Leu (c.1858G>T) is classified Uncertain significance in ACOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely pathogenic (0.5838); Very rare (popmax 0.00186%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACOX1 p.Val620Leu (c.1858G>T)?

ACOX1 p.Val620Leu (c.1858G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACOX1 p.Val620Leu (c.1858G>T) in the general population?

ACOX1 p.Val620Leu (c.1858G>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about ACOX1 p.Val620Leu (c.1858G>T)?

AlphaMissense predicts likely pathogenic (score 0.5838) — an in-silico prediction, not a clinical call.

ACOX1 p.Val620Leu

c.1858G>T · VCV3824593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5838	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -10.11	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.37, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 3,123 bp · p 0.16 · regional, not allelic
Overall
CADD	23.0	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 0.00186% European (non-Finnish) · 22/1,180,032 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00142% 23/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,638
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: ACOX1
Protein: p.Val620Leu
Coding: c.1858G>T
MANE Select: NM_004035
Type: single nucleotide variant
Location: chr17:75948328 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.95

Full ACOX1 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

ACOX1 p.Val620= Likely benign ★ same residue
ACOX1 p.Ala296Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala346Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala375Thr Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala499Ser Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala553Thr Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala571Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Arg122His 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/acox1-p-val620leu (accessed [today's date]).

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