PIN1 p.Pro8=
c.24G>T · rs772645473 · VCV3213096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0279%, 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 -0.37 | GERP -3.7 |
| Overall | ||
| CADD | 10.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0279%
European (non-Finnish) · 318/1,141,718 alleles
Filtering AF
0.0253%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0243%
Overall
0.0235%
357/1,522,278 alleles · ultra-rare
exomes 326/1,370,120 · genomes 31/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0279% | 3,590 |
| African / African-American | 0.017% | 5,876 |
| Remaining individualsnot grpmax-eligible | 0.0152% | 6,589 |
| Admixed American | 0.014% | 7,161 |
| South Asian | 0.0097% | 10,309 |
| East Asian | 0.0077% | 12,995 |
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
- PIN1
- Protein
- p.Pro8=
- Coding
- c.24G>T
- MANE Select
- NM_006221
- dbSNP
- rs772645473
- Type
- single nucleotide variant
- Location
- chr19:9835368 (GRCh38)
- Gene constraint
- LOEUF 1.176 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 92.57 · 194 PDB
- Residue 8
- the ww domain; an α-helix
Similar variants
- PIN1 p.Pro8Leu Uncertain significance ★ ⚠ same residue
- PIN1 p.Pro8Ser Uncertain significance ★ ⚠ same residue
- PIN1 p.Ala140Val Uncertain significance ★ same type
- PIN1 p.Ala53Ser Uncertain significance ★ ⚠ same type
- PIN1 p.Arg119Lys Uncertain significance ★ ⚠ same type
- PIN1 p.Arg74Trp Uncertain significance ★ ⚠ same type
- PIN1 p.Gln109His Uncertain significance ★ ⚠ same type
- PIN1 p.Gln66Glu 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/pin1-p-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown