ADAM9 p.Pro495=
c.1485A>G · rs756295533 · VCV1944747
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.03%, 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 -0.089 | GERP -3.6, phastCons 0.005 |
| Overall | ||
| CADD | 7.938 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.03%
Admixed American · 18/59,962 alleles
Filtering AF
0.0194%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.016%
Overall
0.00143%
23/1,613,692 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.03% | 3,331 |
| European (non-Finnish) | 0.000424% | 235,960 |
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.Pro495=
- Coding
- c.1485A>G
- MANE Select
- NM_003816
- dbSNP
- rs756295533
- Type
- single nucleotide variant
- Location
- chr8:39055666 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.14
- Residue 495
- the disintegrin 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-pro495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown