Is ACSL4 p.Pro627Ser (c.1879C>T) pathogenic?

ACSL4 p.Pro627Ser (c.1879C>T) is classified Uncertain significance in ACSL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely pathogenic (0.987); Absent from gnomAD v4.1.

How common is ACSL4 p.Pro627Ser (c.1879C>T) in the general population?

ACSL4 p.Pro627Ser (c.1879C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSL4 p.Pro627Ser (c.1879C>T)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

ACSL4 p.Pro627Ser

c.1879C>T · VCV3390828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -10.92	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P668S vs ClinVar P627S) — verify the residue.

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: ACSL4
Protein: p.Pro627Ser
Coding: c.1879C>T
MANE Select: NM_001318510
Type: single nucleotide variant
Location: chrX:109644163 (GRCh38)
Structure: AlphaFold pLDDT 90.46

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

Similar variants

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
ACSL4 p.Lys388Arg 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-pro627ser (accessed [today's date]).

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