Is ACSL6 p.Arg604Gln (c.1811G>A) pathogenic?

ACSL6 p.Arg604Gln (c.1811G>A) is classified Uncertain significance in ACSL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1069); Very rare (popmax 0.00134%, afr).

How common is ACSL6 p.Arg604Gln (c.1811G>A) in the general population?

ACSL6 p.Arg604Gln (c.1811G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ACSL6 p.Arg604Gln (c.1811G>A)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

ACSL6 p.Arg604Gln

c.1811G>A · VCV4219464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -7.34	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 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 57 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	29.5	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 R579Q vs ClinVar R604Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,852 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,906 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,852
European (non-Finnish)	0.000678%	147,498

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: ACSL6
Protein: p.Arg604Gln
Coding: c.1811G>A
MANE Select: NM_001009185
Type: single nucleotide variant
Location: chr5:131962581 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.15

Full ACSL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSL6 p.Ala418Ser Uncertain significance ★ ⚠ same type
ACSL6 p.Ala507Val Uncertain significance ★ ⚠ same type
ACSL6 p.Ala609Val Uncertain significance ★ ⚠ same type
ACSL6 p.Arg122Cys Uncertain significance ★ ⚠ same type
ACSL6 p.Arg122His Uncertain significance ★ ⚠ same type
ACSL6 p.Arg182Gln Uncertain significance ★ ⚠ same type
ACSL6 p.Arg212Cys Uncertain significance ★ ⚠ same type
ACSL6 p.Arg336Lys 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/acsl6-p-arg604gln (accessed [today's date]).

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