PROP1 p.Pro42=
c.126C>T · rs1295592162 · VCV2124417
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, sas)
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 0.65 | phastCons 0.001 |
| Overall | ||
| CADD | 2.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
South Asian · 3/90,114 alleles
Filtering AF
0.000884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000445%
Overall
0.000187%
3/1,603,894 alleles · very rare
exomes 3/1,451,594 · genomes 0/152,300 · 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
- PROP1
- Protein
- p.Pro42=
- Coding
- c.126C>T
- MANE Select
- NM_006261
- dbSNP
- rs1295592162
- Type
- single nucleotide variant
- Location
- chr5:177994322 (GRCh38)
- Gene constraint
- LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.74
- Residue 42
- the 'disordered' region
Similar variants
- PROP1 p.Pro42Leu Uncertain significance ★ ⚠ same residue
- PROP1 c.109+1G>A Pathogenic ★★ same type
- PROP1 c.110-2A>G Likely pathogenic ★★ same type
- PROP1 c.343-1G>A Likely pathogenic ★★ same type
- PROP1 p.Arg112Ter Pathogenic/Likely pathogenic ★★ same type
- PROP1 p.Arg120Cys Pathogenic/Likely pathogenic ★★ same type
- PROP1 p.Arg125Gln Likely pathogenic ★★ same type
- PROP1 p.Arg125Trp Pathogenic ★★ 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/prop1-p-pro42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown