Is ACSL6 p.Met26Val (c.76A>G) pathogenic?

ACSL6 p.Met26Val (c.76A>G) is classified Uncertain significance in ACSL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Very rare (popmax 0.00102%, nfe).

How common is ACSL6 p.Met26Val (c.76A>G) in the general population?

ACSL6 p.Met26Val (c.76A>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

ACSL6 p.Met26Val

c.76A>G · VCV4636997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.324	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 57 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,644 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,216 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.Met26Val
Coding: c.76A>G
MANE Select: NM_001009185
Type: single nucleotide variant
Location: chr5:131994225 (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-met26val (accessed [today's date]).

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