ADAM8 p.Ser742=
c.2226G>A · rs374536208 · VCV3146127
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0123%, 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 -6.7 | GERP -2 |
| Overall | ||
| CADD | 0.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0123%
African / African-American · 8/65,088 alleles
Filtering AF
0.00607%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0044%
Overall
0.00222%
28/1,260,784 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0123% | 8,136 |
| Remaining individualsnot grpmax-eligible | 0.00862% | 11,597 |
| South Asian | 0.00389% | 25,698 |
| Admixed American | 0.00384% | 26,044 |
| East Asian | 0.00307% | 32,544 |
| European (non-Finnish) | 0.0013% | 76,657 |
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.Ser742=
- Coding
- c.2226G>A
- MANE Select
- NM_001109
- dbSNP
- rs374536208
- Type
- single nucleotide variant
- Location
- chr10:133267956 (GRCh38)
- Gene constraint
- LOEUF 1.423 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.28 · 1 PDB
- Residue 742
- 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-ser742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown