CLDN19 p.Phe166=
c.498C>T · rs776225389 · VCV875466
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.583 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.6 | GERP -3.4 |
| Overall | ||
| CADD | 1.041 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.018% | 5,543 |
| African / African-Americangrpmax | 0.0162% | 6,187 |
| Admixed American | 0.0132% | 7,596 |
| South Asian | 0.0105% | 9,553 |
| European (non-Finnish) | 0.00835% | 11,978 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- CLDN19
- Protein
- p.Phe166=
- Coding
- c.498C>T
- MANE Select
- NM_148960
- dbSNP
- rs776225389
- Type
- single nucleotide variant
- Location
- chr1:42736006 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.08
Disease context
renal hypomagnesemia 5 with ocular involvement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Primary hypomagnesemia with hypercalciuria and nephrocalcinosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy
Similar variants
- CLDN19 p.Gly20Asp Pathogenic/Likely pathogenic ★★ same condition
- CLDN19 p.Gly75Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CLDN19 p.Leu90Arg Pathogenic/Likely pathogenic ★★ same condition
- CLDN19 p.Pro28Leu Likely pathogenic ★★ same condition
- CLDN19 c.-150C>T Uncertain significance ★★ same condition
- CLDN19 p.Ala216Thr Uncertain significance ★★ ⚠ same condition
- CLDN19 p.Ala218Thr Uncertain significance ★★ ⚠ same condition
- CLDN19 p.Ala55Thr 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/cldn19-p-phe166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown