Is ART5 p.Arg80Gln (c.239G>A) pathogenic?

ART5 p.Arg80Gln (c.239G>A) is classified Uncertain significance in ART5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.033%, mid).

How common is ART5 p.Arg80Gln (c.239G>A) in the general population?

ART5 p.Arg80Gln (c.239G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ART5 p.Arg80Gln (c.239G>A)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

ART5 p.Arg80Gln

c.239G>A · rs149578965 · VCV3129963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.84	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 -5.1	GERP -3.7
Regional constraint	o/e 1.08	unconstrained · MANE · 3,121 bp · p 0.13 · regional, not allelic
Overall
CADD	0.022	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00304% 49/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
East Asian	0.0201%	4,987
African / African-American	0.00666%	15,014
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00254%	39,335
South Asian	0.0011%	91,088

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.Arg80Gln
Coding: c.239G>A
MANE Select: NM_053017
dbSNP: rs149578965
Type: single nucleotide variant
Location: chr11:3640190 (GRCh38)
Gene constraint: LOEUF 1.332 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 80: 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-arg80gln (accessed [today's date]).

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