Is ACSL6 p.Met197Val (c.589A>G) pathogenic?

ACSL6 p.Met197Val (c.589A>G) is classified Uncertain significance in ACSL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.2066); Very rare (popmax 0.000254%, nfe).

How common is ACSL6 p.Met197Val (c.589A>G) in the general population?

ACSL6 p.Met197Val (c.589A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ACSL6 p.Met197Val (c.589A>G)?

AlphaMissense predicts likely benign (score 0.2066) — an in-silico prediction, not a clinical call.

ACSL6 p.Met197Val

c.589A>G · rs2531987317 · VCV3140164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2066	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 57 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	25.0	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 M172V vs ClinVar M197V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,460 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,842 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: ACSL6
Protein: p.Met197Val
Coding: c.589A>G
MANE Select: NM_001009185
dbSNP: rs2531987317
Type: single nucleotide variant
Location: chr5:131988868 (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-met197val (accessed [today's date]).

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