Is ART3 p.Ala155Thr (c.463G>A) pathogenic?

ART3 p.Ala155Thr (c.463G>A) is classified Uncertain significance in ART3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely benign (0.0701); Ultra-rare (popmax 0.0165%, mid).

How common is ART3 p.Ala155Thr (c.463G>A) in the general population?

ART3 p.Ala155Thr (c.463G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ART3 p.Ala155Thr (c.463G>A)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

ART3 p.Ala155Thr

c.463G>A · VCV3433046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -4.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP -1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 6,390 bp · p 0.96 · regional, not allelic
Overall
CADD	12.44	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 0.0165% Middle Eastern · 1/6,060 alleles

Overall 0.000137% 2/1,461,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
European (non-Finnish)	8.47e-05%	1,180,027

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.Ala155Thr
Coding: c.463G>A
MANE Select: NM_001130016
Type: single nucleotide variant
Location: chr4:76082217 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.56
Residue 155: a disulfide bond; the tr mart core domain

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.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
ART3 p.Arg46Gly 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-ala155thr (accessed [today's date]).

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