Is ART3 p.Arg46Gly (c.136A>G) pathogenic?

ART3 p.Arg46Gly (c.136A>G) is classified Uncertain significance in ART3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: ambiguous (0.5348); Very rare (popmax 0.0022%, nfe).

How common is ART3 p.Arg46Gly (c.136A>G) in the general population?

ART3 p.Arg46Gly (c.136A>G) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about ART3 p.Arg46Gly (c.136A>G)?

AlphaMissense predicts ambiguous (score 0.5348) — an in-silico prediction, not a clinical call.

ART3 p.Arg46Gly

c.136A>G · VCV3949872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5348	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 6,390 bp · p 0.96 · regional, not allelic
Overall
CADD	22.6	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

Grpmax group 0.0022% European (non-Finnish) · 26/1,180,054 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00173% 28/1,614,136 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,387
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,944

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: ART3
Protein: p.Arg46Gly
Coding: c.136A>G
MANE Select: NM_001130016
Type: single nucleotide variant
Location: chr4:76081890 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.56
Residue 46: a disulfide bond

Full ART3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CXCL10 p.Ala81= Benign ★★ same type
ART3 p.Ala118Val Uncertain significance ★ ⚠ same type
ART3 p.Ala14Ser Uncertain significance ★ ⚠ same type
ART3 p.Ala155Thr Uncertain significance ★ ⚠ same type
ART3 p.Ala193Gly Uncertain significance ★ ⚠ same type
ART3 p.Ala193Thr Uncertain significance ★ ⚠ same type
ART3 p.Ala382Asp Uncertain significance ★ ⚠ same type
ART3 p.Ala388Asp 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/art3-p-arg46gly (accessed [today's date]).

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