Is ART5 p.Leu64Pro (c.191T>C) pathogenic?

ART5 p.Leu64Pro (c.191T>C) is classified Uncertain significance in ART5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). AlphaMissense: likely pathogenic (0.6903); Absent from gnomAD v4.1.

How common is ART5 p.Leu64Pro (c.191T>C) in the general population?

ART5 p.Leu64Pro (c.191T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ART5 p.Leu64Pro (c.191T>C)?

AlphaMissense predicts likely pathogenic (score 0.6903) — an in-silico prediction, not a clinical call.

ART5 p.Leu64Pro

c.191T>C · rs2494241244 · VCV2276550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6903 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6903	likely pathogenic
REVEL	0.422	indeterminate
SaProt	LLR -14.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 3,121 bp · p 0.13 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Leu64Pro
Coding: c.191T>C
MANE Select: NM_053017
dbSNP: rs2494241244
Type: single nucleotide variant
Location: chr11:3640238 (GRCh38)
Gene constraint: LOEUF 1.332 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 64: 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-leu64pro (accessed [today's date]).

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