ADAM9 p.Val219=
c.657C>T · VCV4697895
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00576%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.23 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.3 |
| Overall | ||
| CADD | 12.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00576%
European (non-Finnish) · 68/1,179,916 alleles
Filtering AF
0.00462%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00423%
Overall
0.00459%
74/1,613,670 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00576% | 17,352 |
| Admixed American | 0.00333% | 29,994 |
| South Asian | 0.00329% | 30,362 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
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
- ADAM9
- Protein
- p.Val219=
- Coding
- c.657C>T
- MANE Select
- NM_003816
- Type
- single nucleotide variant
- Location
- chr8:39018903 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.14
- Residue 219
- the peptidase m12b domain
Similar variants
- ADAM9 p.Tyr213Ter Pathogenic/Likely pathogenic ★★ same type
- ADAM9 c.195+5G>A Uncertain significance ★★ same type
- ADAM9 c.997-3C>G Uncertain significance ★★ same type
- ADAM9 p.Ala145Glu Uncertain significance ★★ ⚠ same type
- ADAM9 p.Ala424Thr Uncertain significance ★★ ⚠ same type
- ADAM9 p.Ala510Thr Uncertain significance ★★ ⚠ same type
- ADAM9 p.Ala534Pro Uncertain significance ★★ ⚠ same type
- ADAM9 p.Arg117Trp 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/adam9-p-val219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown