Is ARNT2 p.Gln594Ter (c.1780C>T) pathogenic?

ARNT2 p.Gln594Ter (c.1780C>T) is classified Pathogenic in ARNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Very rare (popmax 8.47e-05%, nfe); Associated with Webb-Dattani syndrome.

What condition is associated with ARNT2 p.Gln594Ter (c.1780C>T)?

ARNT2 p.Gln594Ter (c.1780C>T) is associated with Webb-Dattani syndrome (ClinVar).

How common is ARNT2 p.Gln594Ter (c.1780C>T) in the general population?

ARNT2 p.Gln594Ter (c.1780C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ARNT2 p.Gln594Ter

c.1780C>T · VCV4277846

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Webb-Dattani syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Overall
CADD	41.0	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 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,874 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: ARNT2
Protein: p.Gln594Ter
Coding: c.1780C>T
MANE Select: NM_014862
Type: single nucleotide variant
Location: chr15:80581266 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 59.49
Residue 594: the 'disordered' region

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

Disease context

Webb-Dattani syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARNT2 p.Arg159Ter Pathogenic/Likely pathogenic ★★ same condition
ARNT2 p.Gly472Ser Uncertain significance ★★ ⚠ same condition
ARNT2 p.Pro334Ser Uncertain significance ★★ ⚠ same condition
ARNT2 c.1513+29G>C Benign ★★ same condition
ARNT2 c.1513+78T>C Benign ★★ same condition
ARNT2 c.1918+18G>A Benign/Likely benign ★★ same condition
ARNT2 c.195-16C>T Benign/Likely benign ★★ same condition
ARNT2 c.726-69T>C Benign ★★ same condition

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-gln594ter (accessed [today's date]).

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