JPH2 p.Ala401=
c.1203G>A · rs138017620 · VCV519075
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
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 -5.5 | GERP -4.1 |
| Overall | ||
| CADD | 5.895 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,006 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00192%
31/1,612,090 alleles · ultra-rare
exomes 29/1,459,852 · genomes 2/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| African / African-American | 0.00534% | 18,737 |
| South Asian | 0.00329% | 30,363 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,236 |
| European (non-Finnish) | 0.00119% | 84,288 |
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.Ala401=
- Coding
- c.1203G>A
- MANE Select
- NM_020433
- dbSNP
- rs138017620
- Type
- single nucleotide variant
- Location
- chr20:44118590 (GRCh38)
- Gene constraint
- LOEUF 1.051 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.09 · 2 PDB
- Residue 401
- an α-helix
Similar variants
- JPH2 p.Ala401Val Uncertain significance ★★ ⚠ 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-ala401 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown