SPINT2 p.Leu79=
c.235C>T · rs769191493 · VCV2900504
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 -0.73 | GERP -3.8 |
| Overall | ||
| CADD | 0.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,078 alleles
Filtering AF
0.000953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00143%
23/1,613,548 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,078 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,235 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.00153% | 65,556 |
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.Leu79=
- Coding
- c.235C>T
- MANE Select
- NM_021102
- dbSNP
- rs769191493
- Type
- single nucleotide variant
- Location
- chr19:38283755 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 1 PDB
- Residue 79
- a disulfide bond; a β-strand; the bpti/kunitz inhibitor 1 domain
Similar variants
- SPINT2 p.Leu79Val Uncertain significance ★★ ⚠ 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
- SPINT2 p.Arg225Gln 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-leu79 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown