JPH2 p.Pro526=
c.1578G>A · rs1425684614 · VCV4076501
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00257%, eas)
Conditions
1
hypertrophic cardiomyopathy
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 -1.4 | GERP -1.3 |
| Overall | ||
| CADD | 4.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00257%
East Asian · 1/38,850 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000267%
4/1,499,762 alleles · very rare
exomes 3/1,347,684 · genomes 1/152,078 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00257% | 38,850 |
| Finnishnot grpmax-eligible | 0.00228% | 43,938 |
| European (non-Finnish) | 0.000176% | 568,120 |
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.Pro526=
- Coding
- c.1578G>A
- MANE Select
- NM_020433
- dbSNP
- rs1425684614
- Type
- single nucleotide variant
- Location
- chr20:44116097 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.09 · 2 PDB
- Residue 526
- the 'disordered' region; a UniProt-annotated variant site (in cmd2e; uncertain significance)
Similar variants
- JPH2 p.Pro526Leu Uncertain significance ★★ ⚠ same residue
- JPH2 p.Pro526Thr Uncertain significance ★ ⚠ same residue
- JPH2 p.Thr161Lys Pathogenic/Likely pathogenic ★★ 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.Ala394Thr Uncertain significance ★★ ⚠ same condition
- JPH2 p.Ala401Val 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-pro526 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown