Is ART3 p.Phe258Ser (c.773T>C) pathogenic?

ART3 p.Phe258Ser (c.773T>C) is classified Uncertain significance in ART3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.9352); Absent from gnomAD v4.1.

How common is ART3 p.Phe258Ser (c.773T>C) in the general population?

ART3 p.Phe258Ser (c.773T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ART3 p.Phe258Ser (c.773T>C)?

AlphaMissense predicts likely pathogenic (score 0.9352) — an in-silico prediction, not a clinical call.

ART3 p.Phe258Ser

c.773T>C · VCV3787826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9352 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9352	likely pathogenic · top 4% in ART3
REVEL	0.151	moderately benign-leaning
SaProt	LLR -3.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 30 kb · p 0.87 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ART3
Protein: p.Phe258Ser
Coding: c.773T>C
MANE Select: NM_001130016
Type: single nucleotide variant
Location: chr4:76082527 (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.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-phe258ser (accessed [today's date]).

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