JPH2 p.Pro603=
c.1809G>A · rs752359114 · VCV1780527
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0045%, eas)
Conditions
2
Cardiovascular phenotype
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 -9.1 | GERP -2 |
| Overall | ||
| CADD | 0.309 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0045%
East Asian · 2/44,400 alleles
Filtering AF
0.00268%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00238%
Overall
0.00278%
44/1,585,434 alleles · very rare
exomes 42/1,433,578 · genomes 2/151,856 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0045% | 22,200 |
| European (non-Finnish) | 0.00359% | 27,893 |
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
- JPH2
- Protein
- p.Pro603=
- Coding
- c.1809G>A
- MANE Select
- NM_020433
- dbSNP
- rs752359114
- Type
- single nucleotide variant
- Location
- chr20:44115866 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.09 · 2 PDB
- Residue 603
- the 'disordered' region; a UniProt-annotated variant site (in cmd2e; uncertain significance)
Similar variants
- JPH2 p.Pro603Leu Likely benign ★★ same residue
- JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ same condition
- JPH2 c.-4T>A Uncertain significance ★★ same condition
- JPH2 p.Ala181Thr Uncertain significance ★★ ⚠ same condition
- JPH2 p.Ala194Ser Uncertain significance ★★ ⚠ same condition
- JPH2 p.Ala214Glu Uncertain significance ★★ ⚠ same condition
- JPH2 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
- JPH2 p.Ala23Val 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/jph2-p-pro603 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown