Is ACSL6 p.Phe417Ser (c.1250T>C) pathogenic?

ACSL6 p.Phe417Ser (c.1250T>C) is classified Uncertain significance in ACSL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-09). AlphaMissense: likely pathogenic (0.6186); Very rare (popmax 0.00534%, afr).

How common is ACSL6 p.Phe417Ser (c.1250T>C) in the general population?

ACSL6 p.Phe417Ser (c.1250T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ACSL6 p.Phe417Ser (c.1250T>C)?

AlphaMissense predicts likely pathogenic (score 0.6186) — an in-silico prediction, not a clinical call.

ACSL6 p.Phe417Ser

c.1250T>C · rs1183880502 · VCV3140124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6186	likely pathogenic
REVEL	0.311	indeterminate
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 57 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	24.9	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 F392S vs ClinVar F417S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,098 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.Phe417Ser
Coding: c.1250T>C
MANE Select: NM_001009185
dbSNP: rs1183880502
Type: single nucleotide variant
Location: chr5:131972812 (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-phe417ser (accessed [today's date]).

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