ARNT2 p.Ala109=
c.327C>T · rs753003138 · VCV1985444
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0512%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.5 | GERP -3.8 |
| Overall | ||
| CADD | 8.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0512%
East Asian · 23/44,892 alleles
Filtering AF
0.035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0296%
Overall
0.00737%
119/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0512% | 1,952 |
| European (non-Finnish) | 0.00754% | 13,259 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| South Asian | 0.00329% | 30,361 |
| African / African-American | 0.00133% | 74,914 |
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.Ala109=
- Coding
- c.327C>T
- MANE Select
- NM_014862
- dbSNP
- rs753003138
- Type
- single nucleotide variant
- Location
- chr15:80470350 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 59.49
- Residue 109
- the bhlh domain
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-ala109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown