ADAM8 p.Pro748=
c.2244G>A · VCV3488544
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0906%, mid)
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 -12 | GERP -2.1 |
| Overall | ||
| CADD | 0.319 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0906%
Middle Eastern · 3/3,310 alleles
Filtering AF
0.031%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0252%
Overall
0.00294%
37/1,259,958 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0906% | 1,103 |
| East Asian | 0.0495% | 2,021 |
| South Asian | 0.0384% | 2,605 |
| Remaining individualsnot grpmax-eligible | 0.00431% | 23,213 |
| Finnishnot grpmax-eligible | 0.0022% | 45,402 |
| African / African-American | 0.00154% | 64,952 |
| European (non-Finnish) | 0.000401% | 249,071 |
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.Pro748=
- Coding
- c.2244G>A
- MANE Select
- NM_001109
- Type
- single nucleotide variant
- Location
- chr10:133267938 (GRCh38)
- Gene constraint
- LOEUF 1.423 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.28 · 1 PDB
- Residue 748
- the 'disordered' region
Similar variants
- ADAM8 p.Pro748Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro748 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown