PCARE p.Pro707=
c.2121A>T · rs199992183 · VCV1079601
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.151%, 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 -3.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.151%
African / African-American · 113/75,070 alleles
Filtering AF
0.128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.12%
Overall
0.00781%
126/1,614,250 alleles · rare
exomes 59/1,461,886 · genomes 67/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.151% | 664 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,814 |
| Admixed American | 0.00666% | 15,007 |
| European (non-Finnish) | 8.47e-05% | 1,180,034 |
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.Pro707=
- Coding
- c.2121A>T
- MANE Select
- NM_001029883
- dbSNP
- rs199992183
- Type
- single nucleotide variant
- Location
- chr2:29072141 (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 707
- the 'disordered' region
Similar variants
- PCARE p.Pro707Ala Uncertain significance ★ ⚠ same residue
- PCARE p.Pro707Leu 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-pro707 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown