Is ART5 p.Leu141Pro (c.422T>C) pathogenic?

ART5 p.Leu141Pro (c.422T>C) is classified Uncertain significance in ART5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.6527); Very rare (popmax 0.00223%, eas).

How common is ART5 p.Leu141Pro (c.422T>C) in the general population?

ART5 p.Leu141Pro (c.422T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ART5 p.Leu141Pro (c.422T>C)?

AlphaMissense predicts likely pathogenic (score 0.6527) — an in-silico prediction, not a clinical call.

ART5 p.Leu141Pro

c.422T>C · VCV3433193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6527	likely pathogenic
REVEL	0.599	indeterminate
SaProt	LLR -15.97	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	25.4	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

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 0.000656% 1/152,346 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: ART5
Protein: p.Leu141Pro
Coding: c.422T>C
MANE Select: NM_053017
Type: single nucleotide variant
Location: chr11:3640007 (GRCh38)
Gene constraint: LOEUF 1.332 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 141: 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.Leu141Val Uncertain significance ★ ⚠ same residue
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

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-leu141pro (accessed [today's date]).

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