Is ART5 p.Pro85Arg (c.254C>G) pathogenic?

ART5 p.Pro85Arg (c.254C>G) is classified Uncertain significance in ART5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.3891); Absent from gnomAD v4.1.

How common is ART5 p.Pro85Arg (c.254C>G) in the general population?

ART5 p.Pro85Arg (c.254C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ART5 p.Pro85Arg (c.254C>G)?

AlphaMissense predicts ambiguous (score 0.3891) — an in-silico prediction, not a clinical call.

ART5 p.Pro85Arg

c.254C>G · VCV3949974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3891	ambiguous
REVEL	0.332	indeterminate
SaProt	LLR -11.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 3,121 bp · p 0.13 · regional, not allelic
Overall
CADD	23.5	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: ART5
Protein: p.Pro85Arg
Coding: c.254C>G
MANE Select: NM_053017
Type: single nucleotide variant
Location: chr11:3640175 (GRCh38)
Gene constraint: LOEUF 1.332 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 85: a disulfide bond; the tr mart core domain

Full ART5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ART5 p.Ser271Thr Benign ★★ same type
ART5 p.Ala113Ser Uncertain significance ★ ⚠ same type
ART5 p.Ala182Thr Uncertain significance ★ ⚠ same type
ART5 p.Ala182Val Uncertain significance ★ ⚠ same type
ART5 p.Ala208Thr Uncertain significance ★ ⚠ same type
ART5 p.Ala22Pro Uncertain significance ★ ⚠ same type
ART5 p.Ala22Thr Uncertain significance ★ ⚠ same type
ART5 p.Ala62Val 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/art5-p-pro85arg (accessed [today's date]).

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