ADAM22 p.Ser399=
c.1197C>T · rs376804868 · VCV2657662
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.32 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -11 |
| Overall | ||
| CADD | 5.448 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
European (non-Finnish) · 283/1,178,606 alleles
Filtering AF
0.0217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0207%
Overall
0.0191%
307/1,611,476 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.024% | 4,165 |
| Admixed American | 0.0117% | 8,541 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,404 |
| African / African-American | 0.008% | 12,493 |
| East Asian | 0.0067% | 14,925 |
| Finnishnot grpmax-eligible | 0.00156% | 63,966 |
| South Asian | 0.00111% | 90,438 |
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.Ser399=
- Coding
- c.1197C>T
- MANE Select
- NM_001324418
- dbSNP
- rs376804868
- Type
- single nucleotide variant
- Location
- chr7:88136008 (GRCh38)
- Gene constraint
- LOEUF 0.518 · pLI 0.55 (gnomAD)
- Structure
- AlphaFold pLDDT 73.17 · 10 PDB
- Residue 399
- a disulfide bond; the peptidase m12b domain; a β-strand
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-ser399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown