PCARE p.Val604=
c.1812G>A · rs545459180 · VCV1087977
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00169%, nfe)
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 -4 | GERP -1.4 |
| Overall | ||
| CADD | 0.834 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00169%
European (non-Finnish) · 20/1,180,044 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.00136%
22/1,614,098 alleles · very rare
exomes 20/1,461,880 · genomes 2/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00169% | 59,002 |
| Admixed American | 0.00167% | 60,010 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
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.Val604=
- Coding
- c.1812G>A
- MANE Select
- NM_001029883
- dbSNP
- rs545459180
- Type
- single nucleotide variant
- Location
- chr2:29072450 (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 604
- the 'disordered' region
Similar variants
- PCARE p.Val604Met 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
- PCARE p.Gln268Ter 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-val604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown