ADA2 p.Leu78=
c.232C>T · rs757225675 · VCV1694259
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
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 0.67 | GERP -1.9 |
| Overall | ||
| CADD | 1.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,070 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,152 alleles · very rare
exomes 3/1,461,878 · genomes 0/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,070 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Leu78=
- Coding
- c.232C>T
- MANE Select
- NM_001282225
- dbSNP
- rs757225675
- Type
- single nucleotide variant
- Location
- chr22:17209446 (GRCh38)
- Structure
- AlphaFold pLDDT 85.04 · 1 PDB
- Residue 78
- the sant domain; an α-helix
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-leu78 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown