ADA2 p.Thr129=
c.387C>T · rs1258338183 · VCV1694261
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
1
autoinflammatory syndrome
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 -0.073 | GERP -0.49, phastCons 0.71 |
| Overall | ||
| CADD | 5.554 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,010 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00031%
5/1,613,806 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,003 |
| European (non-Finnish) | 0.00017% | 589,897 |
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
- ADA2
- Protein
- p.Thr129=
- Coding
- c.387C>T
- MANE Select
- NM_001166105 · reported on NM_001282225
- dbSNP
- rs1258338183
- Type
- single nucleotide variant
- Location
- chr22:17207226 (GRCh38)
- Structure
- AlphaFold pLDDT 85.04 · 1 PDB
Similar variants
- ADA2 p.Arg169Gln Pathogenic/Likely pathogenic ★★ same condition
- ADA2 p.Gly47Arg Pathogenic ★★ same condition
- ADA2 p.His112Gln Pathogenic/Likely pathogenic ★★ same condition
- ADA2 p.Tyr453Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ADA2 p.Ala27Ser Uncertain significance ★★ ⚠ same condition
- ADA2 p.Ala345Pro Uncertain significance ★★ ⚠ same condition
- ADA2 p.Ala35Val Uncertain significance ★★ ⚠ same condition
- ADA2 p.Arg154Cys Uncertain significance ★★ ⚠ 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/ada2-p-thr129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown