Is ARL3 p.Ile123Val (c.367A>G) pathogenic?

ARL3 p.Ile123Val (c.367A>G) is classified Uncertain significance in ARL3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0891); Very rare (popmax 0.00398%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARL3 p.Ile123Val (c.367A>G)?

ARL3 p.Ile123Val (c.367A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARL3 p.Ile123Val (c.367A>G) in the general population?

ARL3 p.Ile123Val (c.367A>G) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about ARL3 p.Ile123Val (c.367A>G)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

ARL3 p.Ile123Val

c.367A>G · rs752095202 · VCV1983052

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.094, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 37 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	15.86	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00398% European (non-Finnish) · 47/1,180,034 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00304% 49/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,107
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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.Ile123Val
Coding: c.367A>G
MANE Select: NM_004311
dbSNP: rs752095202
Type: single nucleotide variant
Location: chr10:102685950 (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

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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-ile123val (accessed [today's date]).

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