Is ARL3 p.Leu130Phe (c.390G>T) pathogenic?

ARL3 p.Leu130Phe (c.390G>T) is classified Uncertain significance in ARL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: ambiguous (0.5128); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARL3 p.Leu130Phe (c.390G>T)?

ARL3 p.Leu130Phe (c.390G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARL3 p.Leu130Phe (c.390G>T) in the general population?

ARL3 p.Leu130Phe (c.390G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARL3 p.Leu130Phe (c.390G>T)?

AlphaMissense predicts ambiguous (score 0.5128) — an in-silico prediction, not a clinical call.

ARL3 p.Leu130Phe

c.390G>T · VCV3785467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5128 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5128	ambiguous
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -12.18	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.2	GERP 0.54, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 37 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARL3
Protein: p.Leu130Phe
Coding: c.390G>T
MANE Select: NM_004311
Type: single nucleotide variant
Location: chr10:102685927 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 92.73

Full ARL3 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

ARL3 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
ARL3 p.Ala179Pro Uncertain significance ★★ ⚠ same condition
ARL3 p.Ala179Thr Uncertain significance ★★ ⚠ same condition
ARL3 p.Arg151Gln Uncertain significance ★★ ⚠ same condition
ARL3 p.Arg8Cys Uncertain significance ★★ ⚠ same condition
ARL3 p.Arg8Leu Uncertain significance ★★ ⚠ same condition
ARL3 p.Asp150Asn Uncertain significance ★★ ⚠ same condition
ARL3 p.Asp86Asn Uncertain significance ★★ ⚠ 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/arl3-p-leu130phe (accessed [today's date]).

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