ADAM9 p.Ala346=
c.1038T>A · rs768414253 · VCV2190188
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 2.9 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 9.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000434%
7/1,614,070 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.00133% | 74,938 |
| European (non-Finnish) | 0.000424% | 236,004 |
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.Ala346=
- Coding
- c.1038T>A
- MANE Select
- NM_003816
- dbSNP
- rs768414253
- Type
- single nucleotide variant
- Location
- chr8:39026718 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.14
- Residue 346
- a disulfide bond; the peptidase m12b domain
Similar variants
- ADAM9 p.Ala346Thr Uncertain significance ★ ⚠ same residue
- 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
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-ala346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown