Is ACSL4 p.Pro636Ser (c.1906C>T) pathogenic?

ACSL4 p.Pro636Ser (c.1906C>T) is classified Uncertain significance in ACSL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-11). AlphaMissense: likely benign (0.2311); Very rare (popmax 0.000112%, nfe).

How common is ACSL4 p.Pro636Ser (c.1906C>T) in the general population?

ACSL4 p.Pro636Ser (c.1906C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ACSL4 p.Pro636Ser (c.1906C>T)?

AlphaMissense predicts likely benign (score 0.2311) — an in-silico prediction, not a clinical call.

ACSL4 p.Pro636Ser

c.1906C>T · rs2520758005 · VCV1710853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2311	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -9.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 34 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	24.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P677S vs ClinVar P636S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,364 alleles

Overall 9.12e-05% 1/1,096,917 alleles · very rare

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.Pro636Ser
Coding: c.1906C>T
MANE Select: NM_001318510
dbSNP: rs2520758005
Type: single nucleotide variant
Location: chrX:109644136 (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-pro636ser (accessed [today's date]).

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