PUS1 p.Pro65=
c.195G>A · rs1257008429 · VCV1610102
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.79e-05%)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.18 | GERP -0.66, phastCons 0.001 |
| Overall | ||
| CADD | 9.925 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.79e-05%
Overall
6.79e-05%
1/1,472,750 alleles · very rare
exomes 1/1,320,406 · genomes 0/152,344 · joint denominator
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
- PUS1
- Protein
- p.Pro65=
- Coding
- c.195G>A
- MANE Select
- NM_025215
- dbSNP
- rs1257008429
- Type
- single nucleotide variant
- Location
- chr12:131930027 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.80 · 6 PDB
- Residue 65
- the 'disordered' region
Similar variants
- PUS1 p.Pro65fs Pathogenic ★ same residue
- PUS1 p.Gln101Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Gln154Ter Pathogenic ★★ same type
- PUS1 p.Lys306Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Trp15Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Trp161Ter Pathogenic/Likely pathogenic ★★ same type
- PUS1 p.Ala226Thr Uncertain significance ★★ ⚠ same type
- PUS1 p.Ala309Val 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/pus1-p-pro65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown