Is ACSL4 p.Gly488= (c.1464A>G) pathogenic?

ACSL4 p.Gly488= (c.1464A>G) is classified Uncertain significance in ACSL4 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-04-01). Very rare (popmax 0.00295%, eas).

How common is ACSL4 p.Gly488= (c.1464A>G) in the general population?

ACSL4 p.Gly488= (c.1464A>G) is very rare (popmax 0.00295%, eas) (gnomAD).

ACSL4 p.Gly488=

c.1464A>G · rs753267680 · VCV807801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00295%, eas)

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 -0.24	GERP 0.63, phastCons 0.52
Overall
CADD	8.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00295% East Asian · 1/33,851 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000274% 3/1,096,103 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00295%	33,851
European (non-Finnish)	0.000224%	446,843

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: ACSL4
Protein: p.Gly488=
Coding: c.1464A>G
MANE Select: NM_001318510
dbSNP: rs753267680
Type: single nucleotide variant
Location: chrX:109663329 (GRCh38)
Structure: AlphaFold pLDDT 90.46

Full ACSL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSL4 p.Gly488Arg Uncertain significance ★ ⚠ same residue
ACSL4 p.Arg631Gln Uncertain significance ★★ ⚠ same type
ACSL4 p.Asn95Asp Uncertain significance ★★ ⚠ same type
ACSL4 p.Asn95Ser Uncertain significance ★★ ⚠ same type
ACSL4 p.Asp521Asn Uncertain significance ★★ ⚠ same type
ACSL4 p.His150Leu Uncertain significance ★★ ⚠ same type
ACSL4 p.His23Arg Uncertain significance ★★ ⚠ same type
ACSL4 p.Lys271Arg Uncertain significance ★★ ⚠ same type

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/acsl4-p-gly488 (accessed [today's date]).

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