CLDN14 p.Pro197=
c.591G>A · rs374840285 · VCV748472
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, 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 -1.6 | GERP -0.11 |
| Overall | ||
| CADD | 6.826 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/75,048 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00223%
36/1,614,094 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,505 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| South Asian | 0.00769% | 13,011 |
| East Asian | 0.00446% | 22,436 |
| Admixed American | 0.00333% | 30,013 |
| European (non-Finnish) | 0.000847% | 117,998 |
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
- CLDN14
- Protein
- p.Pro197=
- Coding
- c.591G>A
- MANE Select
- NM_001146079
- dbSNP
- rs374840285
- Type
- single nucleotide variant
- Location
- chr21:36461105 (GRCh38)
- Gene constraint
- LOEUF 1.745 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 80.00
- Residue 197
- the 'disordered' region
Similar variants
- CLDN14 p.Pro197Leu Uncertain significance ★ same residue
- CLDN14 p.Pro197fs Pathogenic ★ same residue
- CLDN14 p.Arg81His Pathogenic/Likely pathogenic ★★ same type
- CLDN14 p.Cys97Ter Pathogenic/Likely pathogenic ★★ same type
- CLDN14 p.Trp30Ter Pathogenic/Likely pathogenic ★★ same type
- CLDN14 c.*107G>A Uncertain significance ★★ same type
- CLDN14 p.Ala196Val Uncertain significance ★★ ⚠ same type
- CLDN14 p.Ala72Val 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/cldn14-p-pro197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown