ADAM8 p.Pro732=
c.2196G>A · VCV4005648
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, afr)
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 -0.086 | GERP -2.1 |
| Overall | ||
| CADD | 2.546 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
African / African-American · 11/65,062 alleles
Filtering AF
0.00944%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00749%
Overall
0.00912%
115/1,260,562 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0169% | 5,915 |
| Remaining individualsnot grpmax-eligible | 0.0151% | 6,632 |
| European (non-Finnish) | 0.00964% | 10,376 |
| South Asian | 0.00389% | 25,684 |
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
- ADAM8
- Protein
- p.Pro732=
- Coding
- c.2196G>A
- MANE Select
- NM_001109
- Type
- single nucleotide variant
- Location
- chr10:133267986 (GRCh38)
- Gene constraint
- LOEUF 1.423 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.28 · 1 PDB
- Residue 732
- the 'disordered' region
Similar variants
- ADAM8 p.Ala118= Benign ★★ same type
- ADAM8 p.Ala490Thr Benign ★★ same type
- ADAM8 p.Arg36His Benign ★★ ⚠ same type
- ADAM8 p.Arg433Cys Benign ★★ ⚠ same type
- ADAM8 c.228-2A>G Uncertain significance ★ same type
- ADAM8 p.Ala119Ser Uncertain significance ★ ⚠ same type
- ADAM8 p.Ala119Thr Uncertain significance ★ ⚠ same type
- ADAM8 p.Ala164Ser Uncertain significance ★ ⚠ 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/adam8-p-pro732 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown