SPINT2 p.Val25=
c.75C>A · rs1353814439 · VCV1947223
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00297%, nfe)
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 -0.96 | GERP -3 |
| Overall | ||
| CADD | 2.896 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00297%
European (non-Finnish) · 34/1,145,098 alleles
Filtering AF
0.00214%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00189%
Overall
0.00241%
37/1,535,236 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00297% | 33,679 |
| South Asian | 0.00239% | 41,903 |
| Finnishnot grpmax-eligible | 0.0021% | 47,730 |
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.Val25=
- Coding
- c.75C>A
- MANE Select
- NM_021102
- dbSNP
- rs1353814439
- Type
- single nucleotide variant
- Location
- chr19:38264967 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 1 PDB
Similar variants
- 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
- SPINT2 p.Arg233Cys 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-val25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown