Is ACSL4 p.Tyr82Phe (c.245A>T) pathogenic?

ACSL4 p.Tyr82Phe (c.245A>T) is classified Likely benign in ACSL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-02). AlphaMissense: likely benign (0.2454); Ultra-rare (popmax 0.0128%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACSL4 p.Tyr82Phe (c.245A>T)?

ACSL4 p.Tyr82Phe (c.245A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACSL4 p.Tyr82Phe (c.245A>T) in the general population?

ACSL4 p.Tyr82Phe (c.245A>T) is ultra-rare (popmax 0.0128%, nfe) (gnomAD).

What do computational predictors say about ACSL4 p.Tyr82Phe (c.245A>T)?

AlphaMissense predicts likely benign (score 0.2454) — an in-silico prediction, not a clinical call.

ACSL4 p.Tyr82Phe

c.245A>T · rs372250472 · VCV210087

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2454 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2454	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,257 bp · p 0.0019 · regional, not allelic
Overall
CADD	25.8	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 Y123F vs ClinVar Y82F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% European (non-Finnish) · 114/893,875 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.0101% 122/1,208,731 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0147%	6,794
European (non-Finnish)grpmax	0.0128%	7,841
Finnishnot grpmax-eligible	0.00215%	46,613

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr82Phe
Coding: c.245A>T
MANE Select: NM_001318510
dbSNP: rs372250472
Type: single nucleotide variant
Location: chrX:109682880 (GRCh38)
Structure: AlphaFold pLDDT 90.46

Full ACSL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACSL4 p.Asn95Asp Uncertain significance ★★ ⚠ same condition
ACSL4 p.Asn95Ser Uncertain significance ★★ ⚠ same condition
ACSL4 p.His23Arg Uncertain significance ★★ ⚠ same condition
ACSL4 p.Pro404Leu Uncertain significance ★★ ⚠ same condition
ACSL4 p.Ser501Tyr Uncertain significance ★★ ⚠ same condition
ACSL4 p.Tyr132Cys Uncertain significance ★★ ⚠ same condition
ACSL4 p.Asn153Ser Benign/Likely benign ★★ ⚠ same condition
ACSL4 p.Asp503= Likely benign ★★ same condition

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-tyr82phe (accessed [today's date]).

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