Is ARNT2 p.Arg262fs (c.784dup) pathogenic?

ARNT2 p.Arg262fs (c.784dup) is classified Uncertain significance in ARNT2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-08). Very rare (popmax 0.00161%, nfe); Associated with ARNT2-related disorder.

What condition is associated with ARNT2 p.Arg262fs (c.784dup)?

ARNT2 p.Arg262fs (c.784dup) is associated with ARNT2-related disorder (ClinVar).

How common is ARNT2 p.Arg262fs (c.784dup) in the general population?

ARNT2 p.Arg262fs (c.784dup) is very rare (popmax 0.00161%, nfe) (gnomAD).

ARNT2 p.Arg262fs

c.784dup · VCV3352761

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

ARNT2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.8, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,240 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,613,090 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,065
African / African-American	0.00134%	74,874

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: ARNT2
Protein: p.Arg262fs
Coding: c.784dup
MANE Select: NM_014862
Type: Duplication
Location: chr15:80513965 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 59.49

Full ARNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARNT2-related disorder

Similar variants

ARNT2 p.Arg262Lys Uncertain significance ★★ ⚠ same residue
ARNT2 p.Arg262Met Uncertain significance ★ ⚠ same residue
ARNT2 p.Thr124= Likely benign same condition
ARNT2 p.Gln305fs Pathogenic ★ same type
ARNT2 c.1390-4dup Likely benign ★ same type
ARNT2 c.2055+27_2055+46dup Benign ★ same type
ARNT2 p.Tyr459fs 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/arnt2-p-arg262fs (accessed [today's date]).

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