SPINT2 p.Asn57=
c.171T>C · rs755846896 · VCV1612544
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0274%, sas)
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 -0.36 | GERP -1.5, phastCons 0.27 |
| Overall | ||
| CADD | 7.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0274%
South Asian · 25/91,082 alleles
Filtering AF
0.019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0163%
Overall
0.00229%
37/1,614,038 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0274% | 3,643 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Admixed American | 0.00333% | 29,992 |
| East Asian | 0.00223% | 44,890 |
| European (non-Finnish) | 0.000339% | 295,011 |
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
- SPINT2
- Protein
- p.Asn57=
- Coding
- c.171T>C
- MANE Select
- NM_021102
- dbSNP
- rs755846896
- Type
- single nucleotide variant
- Location
- chr19:38283691 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 1 PDB
- Residue 57
- a disulfide bond; a β-strand; the bpti/kunitz inhibitor 1 domain
Similar variants
- SPINT2 p.Asn57Ser Uncertain significance ★ ⚠ same residue
- SPINT2 p.Asn57fs Pathogenic ★★ same residue
- SPINT2 p.Tyr163Cys Pathogenic ★★ same type
- SPINT2 p.Ala2Val Uncertain significance ★★ ⚠ same type
- SPINT2 p.Ala89Val Uncertain significance ★★ ⚠ same type
- SPINT2 p.Arg182Cys Uncertain significance ★★ ⚠ same type
- SPINT2 p.Arg182His Uncertain significance ★★ ⚠ same type
- SPINT2 p.Arg185Cys 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/spint2-p-asn57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown