ADAMTS3 p.Ser774=
c.2322G>T · rs771401796 · VCV2654806
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0826%, 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 -7.5 | GERP -4.5 |
| Overall | ||
| CADD | 0.259 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0826%
Middle Eastern · 5/6,054 alleles
Filtering AF
0.0325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0211%
Overall
0.00917%
148/1,613,702 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0826% | 1,211 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| European (non-Finnish) | 0.0109% | 9,217 |
| Admixed American | 0.00333% | 29,993 |
| East Asian | 0.00223% | 44,846 |
| African / African-American | 0.00133% | 75,004 |
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
- ADAMTS3
- Protein
- p.Ser774=
- Coding
- c.2322G>T
- MANE Select
- NM_014243
- dbSNP
- rs771401796
- Type
- single nucleotide variant
- Location
- chr4:72304019 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.31
- Residue 774
- the 'spacer' region
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-ser774 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown