ADAMTS3 p.Arg414=
c.1242G>A · rs201105948 · VCV3043969
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.152%, eas)
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 0.42 | GERP 0.49, phastCons 0.99 |
| Overall | ||
| CADD | 8.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.152%
East Asian · 68/44,806 alleles
Filtering AF
0.123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.112%
Overall
0.00775%
125/1,613,878 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.152% | 659 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| Admixed American | 0.0233% | 4,284 |
| African / African-American | 0.00533% | 18,762 |
| South Asian | 0.0022% | 45,534 |
| European (non-Finnish) | 8.48e-05% | 1,179,910 |
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
- ADAMTS3
- Protein
- p.Arg414=
- Coding
- c.1242G>A
- MANE Select
- NM_014243
- dbSNP
- rs201105948
- Type
- single nucleotide variant
- Location
- chr4:72319442 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.31
- Residue 414
- a disulfide bond; the peptidase m12b domain
Similar variants
- ADAMTS3 p.Arg1035Gln Uncertain significance ★★ ⚠ same type
- ADAMTS3 p.Asn1016Ser Uncertain significance ★★ ⚠ same type
- ADAMTS3 c.1746-5T>G Benign/Likely benign ★★ same type
- ADAMTS3 c.2179+21G>A Benign ★★ same type
- ADAMTS3 c.661+7G>A Benign/Likely benign ★★ same type
- ADAMTS3 p.Ala336= Likely benign ★★ same type
- ADAMTS3 p.Arg138Lys Benign ★★ same type
- ADAMTS3 p.Arg565Gln Likely benign ★★ ⚠ 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/adamts3-p-arg414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown