ARNT2 p.Pro678=
c.2034C>T · rs140703832 · VCV1909759
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP 0.44 |
| Overall | ||
| CADD | 11.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/75,048 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00211%
34/1,614,046 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,505 |
| South Asian | 0.00769% | 13,010 |
| Admixed American | 0.00333% | 30,005 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 0.00119% | 84,281 |
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.Pro678=
- Coding
- c.2034C>T
- MANE Select
- NM_014862
- dbSNP
- rs140703832
- Type
- single nucleotide variant
- Location
- chr15:80591683 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 59.49
- Residue 678
- the 'disordered' region
Similar variants
- ARNT2 p.Arg159Ter Pathogenic/Likely pathogenic ★★ same type
- ARNT2 p.Ala483Val Uncertain significance ★★ ⚠ same type
- ARNT2 p.Arg262Lys Uncertain significance ★★ ⚠ same type
- ARNT2 p.Asp705Tyr Uncertain significance ★★ ⚠ same type
- ARNT2 p.Gln520Arg Uncertain significance ★★ ⚠ same type
- ARNT2 p.Gly472Ser Uncertain significance ★★ ⚠ same type
- ARNT2 p.Gly546Arg Uncertain significance ★★ ⚠ same type
- ARNT2 p.Ile347Phe 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/arnt2-p-pro678 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown