JPH3 p.Ser246=
c.738C>T · rs34442559 · VCV710403
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.08%, 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 0.099 | GERP -1.9, phastCons 0.92 |
| Overall | ||
| CADD | 10.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.08%
African / African-American · 2,315/75,042 alleles
Filtering AF
2.98%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.94%
Overall
0.665%
10,724/1,612,686 alleles · low-frequency
exomes 8,951/1,460,412 · genomes 1,773/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.08% | 32 |
| South Asian | 0.632% | 158 |
| European (non-Finnish) | 0.599% | 167 |
| Remaining individualsnot grpmax-eligible | 0.494% | 202 |
| Finnishnot grpmax-eligible | 0.46% | 217 |
| Middle Eastern | 0.264% | 379 |
| Admixed American | 0.232% | 432 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0507% | 1,973 |
| East Asian | 0.00223% | 44,850 |
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
- JPH3
- Protein
- p.Ser246=
- Coding
- c.738C>T
- MANE Select
- NM_020655
- dbSNP
- rs34442559
- Type
- single nucleotide variant
- Location
- chr16:87644613 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.52
- Residue 246
- the 'disordered' region
Similar variants
- JPH3 p.Arg319Trp Uncertain significance ★★ ⚠ same type
- JPH3 p.Leu266Val Uncertain significance ★★ ⚠ same type
- JPH3 p.Thr175Met Uncertain significance ★★ ⚠ same type
- JPH3 c.2167-9C>G Benign/Likely benign ★★ same type
- JPH3 p.Ala271= Benign/Likely benign ★★ same type
- JPH3 p.Ala366= Likely benign ★★ same type
- JPH3 p.Ala384= Likely benign ★★ same type
- JPH3 p.Ala523= Benign/Likely benign ★★ 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/jph3-p-ser246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown