JPH3 p.Ser228=
c.684G>A · rs3751725 · VCV3059953
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 36.7%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
JPH3-related disorder
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 -12 | GERP -5.3 |
| Overall | ||
| CADD | 0.539 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.7%
East Asian · 16,431/44,776 alleles
Filtering AF
36.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 36%
Overall
22.3%
359,524/1,612,710 alleles · common
exomes 330,839/1,460,656 · genomes 28,685/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 36.7% | 3 |
| Finnishnot grpmax-eligible | 25.1% | 4 |
| Amishnot grpmax-eligible | 23.8% | 4 |
| European (non-Finnish) | 23.3% | 4 |
| Admixed American | 22.5% | 4 |
| Remaining individualsnot grpmax-eligible | 20.6% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 16.8% | 6 |
| South Asian | 16.7% | 6 |
| Middle Eastern | 7.69% | 13 |
| African / African-American | 6.96% | 14 |
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.Ser228=
- Coding
- c.684G>A
- MANE Select
- NM_020655
- dbSNP
- rs3751725
- Type
- single nucleotide variant
- Location
- chr16:87644559 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.52
Disease context
JPH3-related disorder
Similar variants
- JPH3 p.Ser228Leu Uncertain significance ★ ⚠ same residue
- JPH3 c.382+635C>T Likely benign same condition
- JPH3 p.Ala154Pro Likely benign same condition
- JPH3 p.Ala190= Likely benign same condition
- JPH3 p.Arg320= Benign same condition
- JPH3 p.Asn103= Likely benign same condition
- JPH3 p.Asp641Tyr Likely benign same condition
- JPH3 p.Ile280= Likely benign 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/jph3-p-ser228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown