PCARE p.Pro475=
c.1425G>A · rs755455124 · VCV1980765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
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 -0.029 | GERP -0.29 |
| Overall | ||
| CADD | 6.786 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,896 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000929%
15/1,614,016 alleles · very rare
exomes 13/1,461,892 · genomes 2/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,448 |
| Admixed American | 0.00333% | 30,003 |
| South Asian | 0.0022% | 45,540 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 0.000678% | 147,504 |
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
- PCARE
- Protein
- p.Pro475=
- Coding
- c.1425G>A
- MANE Select
- NM_001029883
- dbSNP
- rs755455124
- Type
- single nucleotide variant
- Location
- chr2:29072837 (GRCh38)
- Gene constraint
- LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 44.15 · 1 PDB
- Residue 475
- the 'disordered' region
Similar variants
- PCARE p.Pro475Gln Uncertain significance ★ ⚠ same residue
- PCARE p.Pro475Leu Uncertain significance ★ ⚠ same residue
- PCARE c.3668+2T>C Likely pathogenic ★★ same type
- PCARE p.Arg1202Ter Pathogenic/Likely pathogenic ★★ same type
- PCARE p.Arg425Ter Pathogenic ★★ same type
- PCARE p.Arg613Ter Pathogenic ★★ same type
- PCARE p.Arg984Ter Pathogenic ★★ same type
- PCARE p.Gln1097Ter Pathogenic/Likely 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/pcare-p-pro475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown