JPH3 p.Ile280=
c.840C>T · rs147830852 · VCV3052698
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0496%, mid)
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 -2 | GERP -2.1 |
| Overall | ||
| CADD | 9.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0496%
Middle Eastern · 3/6,054 alleles
Filtering AF
0.0299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0288%
Overall
0.0276%
442/1,601,762 alleles · ultra-rare
exomes 419/1,459,854 · genomes 23/141,908 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0496% | 2,018 |
| European (non-Finnish) | 0.0326% | 3,070 |
| Remaining individualsnot grpmax-eligible | 0.0289% | 3,460 |
| Admixed American | 0.0186% | 5,380 |
| South Asian | 0.0177% | 5,646 |
| African / African-American | 0.0098% | 10,204 |
| East Asian | 0.00675% | 14,804 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,302 |
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.Ile280=
- Coding
- c.840C>T
- MANE Select
- NM_020655
- dbSNP
- rs147830852
- Type
- single nucleotide variant
- Location
- chr16:87644715 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.52
Disease context
JPH3-related disorder
Similar variants
- JPH3 p.Ile280Ser 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.Leu177= 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-ile280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown