PCARE p.Pro177=
c.531G>A · rs200914951 · VCV730821
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.198%, mid)
Conditions
1
inherited retinal dystrophy
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 -14 | GERP -3 |
| Overall | ||
| CADD | 0.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.198%
Middle Eastern · 12/6,062 alleles
Filtering AF
0.114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0895%
Overall
0.015%
242/1,614,142 alleles · rare
exomes 214/1,461,892 · genomes 28/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.198% | 505 |
| African / African-American | 0.103% | 974 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| East Asian | 0.029% | 3,453 |
| South Asian | 0.0176% | 5,691 |
| European (non-Finnish) | 0.00856% | 11,683 |
| Admixed American | 0.00333% | 30,012 |
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.Pro177=
- Coding
- c.531G>A
- MANE Select
- NM_001029883
- dbSNP
- rs200914951
- Type
- single nucleotide variant
- Location
- chr2:29073731 (GRCh38)
- Gene constraint
- LOEUF 1.032 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 44.15 · 1 PDB
Similar variants
- PCARE p.Pro177Leu Conflicting classifications of pathogenicity ★ same residue
- PCARE c.3668+2T>C Likely pathogenic ★★ same condition
- PCARE p.Arg984Ter Pathogenic ★★ same condition
- PCARE p.Leu307Ter Pathogenic/Likely pathogenic ★★ same condition
- PCARE p.Trp1001Ter Pathogenic/Likely pathogenic ★★ same condition
- PCARE p.Trp720Ter Pathogenic/Likely pathogenic ★★ same condition
- PCARE p.Trp941Ter Pathogenic/Likely pathogenic ★★ same condition
- PCARE p.Arg1177Gln Uncertain significance ★★ ⚠ same condition
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-pro177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown