Is ART3 p.Ala14Ser (c.40G>T) pathogenic?

ART3 p.Ala14Ser (c.40G>T) is classified Uncertain significance in ART3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.1331); Very rare (popmax 0.000659%).

How common is ART3 p.Ala14Ser (c.40G>T) in the general population?

ART3 p.Ala14Ser (c.40G>T) is very rare (popmax 0.000659%) (gnomAD).

What do computational predictors say about ART3 p.Ala14Ser (c.40G>T)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

ART3 p.Ala14Ser

c.40G>T · rs776853474 · VCV2614113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000659%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.15	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 3.9	GERP -1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 6,390 bp · p 0.96 · regional, not allelic
Overall
CADD	14.46	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 0.000659%

Overall 0.000659% 1/151,806 alleles · very rare

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.Ala14Ser
Coding: c.40G>T
MANE Select: NM_001130016
dbSNP: rs776853474
Type: single nucleotide variant
Location: chr4:76075929 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.56

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.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
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-ala14ser (accessed [today's date]).

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