Is ARL3 p.Arg151Gln (c.452G>A) pathogenic?

ARL3 p.Arg151Gln (c.452G>A) is classified Uncertain significance in ARL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.6123); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARL3 p.Arg151Gln (c.452G>A)?

ARL3 p.Arg151Gln (c.452G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARL3 p.Arg151Gln (c.452G>A) in the general population?

ARL3 p.Arg151Gln (c.452G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARL3 p.Arg151Gln (c.452G>A)?

AlphaMissense predicts likely pathogenic (score 0.6123) — an in-silico prediction, not a clinical call.

ARL3 p.Arg151Gln

c.452G>A · rs376018992 · VCV1899445

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6123	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 37 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

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

Overall 0.000805% 13/1,613,924 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
European (non-Finnish)	0.00102%	98,332

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: ARL3
Protein: p.Arg151Gln
Coding: c.452G>A
MANE Select: NM_004311
dbSNP: rs376018992
Type: single nucleotide variant
Location: chr10:102685865 (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.Arg151Ter Uncertain significance ★★ same residue
ARL3 p.Arg151= Likely benign ★ same residue
ARL3 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
ARL3 p.Ala179Pro Uncertain significance ★★ ⚠ same condition
ARL3 p.Ala179Thr 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

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-arg151gln (accessed [today's date]).

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