Is ARTN p.Pro100Thr (c.298C>A) pathogenic?

ARTN p.Pro100Thr (c.298C>A) is classified Uncertain significance in ARTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.0135%, amr).

How common is ARTN p.Pro100Thr (c.298C>A) in the general population?

ARTN p.Pro100Thr (c.298C>A) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about ARTN p.Pro100Thr (c.298C>A)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

ARTN p.Pro100Thr

c.298C>A · rs931575180 · VCV2457660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -9.01	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 -0.64	GERP -1.9
Regional constraint	o/e 0.87	unconstrained · MANE · 1,105 bp · p 0.015 · regional, not allelic
Overall
CADD	8.74	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 0.0135% Admixed American · 3/22,240 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00584% 70/1,199,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0135%	7,413
European (non-Finnish)	0.00661%	15,122
African / African-American	0.00318%	31,414
Remaining individualsnot grpmax-eligible	0.00231%	43,362

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: ARTN
Protein: p.Pro100Thr
Coding: c.298C>A
MANE Select: NM_057091
dbSNP: rs931575180
Type: single nucleotide variant
Location: chr1:43936400 (GRCh38)
Gene constraint: LOEUF 1.206 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 100: the 'disordered' region

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

Similar variants

NBN p.Gly100Ter Pathogenic ★★ same residue
NBN p.Gly100Ala Uncertain significance ★ ⚠ same residue
NBN p.Gly100= Likely benign ★ same residue
NBN c.1124+1G>C Likely pathogenic ★★ same type
NBN c.1124+2T>G Likely pathogenic ★★ same type
NBN c.1397+2T>A Likely pathogenic ★★ same type
NBN c.171+1G>A Likely pathogenic ★★ same type
NBN c.172-1G>T Likely pathogenic ★★ 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/artn-p-pro100thr (accessed [today's date]).

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