ADAM22 p.Pro172=
c.516A>G · rs1040797874 · VCV2657661
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -0.65 | GERP -4 |
| Overall | ||
| CADD | 7.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,996 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00186%
30/1,613,874 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,999 |
| European (non-Finnish) | 0.0022% | 45,381 |
| African / African-American | 0.00133% | 74,924 |
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.Pro172=
- Coding
- c.516A>G
- MANE Select
- NM_001324418
- dbSNP
- rs1040797874
- Type
- single nucleotide variant
- Location
- chr7:88114626 (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-pro172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown