ADAM22 p.Ala266=
c.798G>A · rs371867819 · VCV721588
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0847%, 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 -5.4 | GERP -12 |
| Overall | ||
| CADD | 5.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0847%
East Asian · 38/44,848 alleles
Filtering AF
0.0634%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.056%
Overall
0.0172%
277/1,612,972 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0847% | 1,180 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,461 |
| European (non-Finnish) | 0.0175% | 5,725 |
| African / African-American | 0.012% | 8,317 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,858 |
| Finnishnot grpmax-eligible | 0.00782% | 12,793 |
| Admixed American | 0.00167% | 59,936 |
| South Asian | 0.0011% | 90,998 |
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
- ADAM22
- Protein
- p.Ala266=
- Coding
- c.798G>A
- MANE Select
- NM_001324418
- dbSNP
- rs371867819
- Type
- single nucleotide variant
- Location
- chr7:88130432 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.55 (gnomAD)
- Structure
- AlphaFold pLDDT 73.17 · 10 PDB
- Residue 266
- an α-helix; the peptidase m12b domain
Similar variants
- ADAM22 p.Ala266Val Uncertain significance ★ ⚠ same residue
- ADAM22 p.Arg513Ser Uncertain significance ★★ ⚠ same type
- ADAM22 p.Gly164Arg Uncertain significance ★★ ⚠ same type
- ADAM22 p.Pro525Thr Uncertain significance ★★ ⚠ same type
- ADAM22 p.Thr713Ser Uncertain significance ★★ ⚠ same type
- ADAM22 p.Tyr57Cys Uncertain significance ★★ ⚠ same type
- ADAM22 p.Val259Ile Uncertain significance ★★ ⚠ same type
- ADAM22 c.1393-3T>C Benign ★★ 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/adam22-p-ala266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown