Is ACSL4 p.Arg529Ser (c.1585C>A) pathogenic?

ACSL4 p.Arg529Ser (c.1585C>A) is classified Pathogenic in ACSL4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-04-01). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 63.

What condition is associated with ACSL4 p.Arg529Ser (c.1585C>A)?

ACSL4 p.Arg529Ser (c.1585C>A) is associated with intellectual disability, X-linked 63 (ClinVar).

How common is ACSL4 p.Arg529Ser (c.1585C>A) in the general population?

ACSL4 p.Arg529Ser (c.1585C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSL4 p.Arg529Ser (c.1585C>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

ACSL4 p.Arg529Ser

c.1585C>A · rs122458138 · VCV11564

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,146,947)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 63

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 1% in ACSL4
REVEL	0.721	pathogenic-leaning
SaProt	LLR -14.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R570S vs ClinVar R529S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,146,947). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACSL4
Protein: p.Arg529Ser
Coding: c.1585C>A
MANE Select: NM_001318510
dbSNP: rs122458138
Type: single nucleotide variant
Location: chrX:109661643 (GRCh38)
Structure: AlphaFold pLDDT 90.46

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

Disease context

intellectual disability, X-linked 63 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACSL4 p.Arg529His Conflicting classifications of pathogenicity ★ ⚠ same residue
ACSL4 p.Arg529Gly Uncertain significance ★ ⚠ same residue
ACSL4 p.Arg631Gln Uncertain significance ★★ ⚠ same condition
ACSL4 p.Asp521Asn Uncertain significance ★★ ⚠ same condition
ACSL4 p.His23Arg Uncertain significance ★★ ⚠ same condition
ACSL4 p.Lys271Arg Uncertain significance ★★ ⚠ same condition
ACSL4 p.Lys388Arg Uncertain significance ★★ ⚠ same condition
ACSL4 p.Ser501Tyr 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/acsl4-p-arg529ser (accessed [today's date]).

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