ADAM22 p.Ala757=
c.2271G>A · rs375592711 · VCV748893
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.13 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -3.6 |
| Overall | ||
| CADD | 6.631 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,048 alleles
Filtering AF
0.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00949%
Overall
0.00992%
160/1,612,456 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,048 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,800 |
| European (non-Finnish) | 0.0117% | 8,543 |
| South Asian | 0.00879% | 11,379 |
| Finnishnot grpmax-eligible | 0.00469% | 21,310 |
| East Asian | 0.00223% | 44,802 |
| Admixed American | 0.00167% | 59,940 |
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.Ala757=
- Coding
- c.2271G>A
- MANE Select
- NM_001324418
- dbSNP
- rs375592711
- Type
- single nucleotide variant
- Location
- chr7:88168216 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.55 (gnomAD)
- Structure
- AlphaFold pLDDT 73.17 · 10 PDB
Similar variants
- 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
- ADAM22 c.1567-4C>T Likely 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-ala757 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown