SPINT2 p.Phe205=
c.615C>T · VCV4738870
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, 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 -3.6 | GERP -4.6 |
| Overall | ||
| CADD | 8.502 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,862 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00178%
26/1,460,684 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,862 |
| South Asian | 0.0022% | 45,500 |
| European (non-Finnish) | 0.00195% | 51,301 |
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.Phe205=
- Coding
- c.615C>T
- MANE Select
- NM_021102
- Type
- single nucleotide variant
- Location
- chr19:38291862 (GRCh38)
- Gene constraint
- LOEUF 0.935 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 1 PDB
- Residue 205
- a UniProt-annotated variant site (in diar3; likely pathogenic)
Similar variants
- SPINT2 p.Phe205Leu 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-phe205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown