CLDN19 p.Val224=
c.672G>A · VCV3657730
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -0.001 | GERP -1.4, phastCons 0.78 |
| Overall | ||
| CADD | 7.949 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,000 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.00048%
7/1,459,236 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,500 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,396 |
| European (non-Finnish) | 0.00034% | 294,440 |
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.Val224=
- Coding
- c.672G>A
- MANE Select
- NM_148960
- Type
- single nucleotide variant
- Location
- chr1:42735089 (GRCh38)
- Gene constraint
- LOEUF 1.254 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.08
- Residue 224
- the 'disordered' region
Similar variants
- CLDN19 p.Val224Glu Uncertain significance ★★ ⚠ same residue
- CLDN19 p.Gly20Asp Pathogenic/Likely pathogenic ★★ same type
- CLDN19 p.Gly75Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
- CLDN19 p.Leu90Arg Pathogenic/Likely pathogenic ★★ same type
- CLDN19 p.Pro28Leu Likely pathogenic ★★ same type
- CLDN19 c.-150C>T Uncertain significance ★★ same type
- CLDN19 p.Ala216Thr Uncertain significance ★★ ⚠ same type
- CLDN19 p.Ala218Thr Uncertain significance ★★ ⚠ 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/cldn19-p-val224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown