PCARE p.Pro377=
c.1131C>G · rs1236713028 · VCV1638381
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 -0.48 | GERP -3.3 |
| Overall | ||
| CADD | 0.351 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,988 alleles
Overall
0.000124%
2/1,614,056 alleles · very rare
exomes 2/1,461,892 · genomes 0/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,988 |
| European (non-Finnish) | 8.47e-05% | 1,180,018 |
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.Pro377=
- Coding
- c.1131C>G
- MANE Select
- NM_001029883
- dbSNP
- rs1236713028
- Type
- single nucleotide variant
- Location
- chr2:29073131 (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 377
- the 'disordered' region
Similar variants
- 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
- PCARE p.Gln268Ter Pathogenic ★★ same type
- PCARE p.Gln610Ter 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-pro377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown