CLDN1 p.Lys65=
c.195A>G · rs145197251 · VCV289199
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.243%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.29 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -0.064, phastCons 1 |
| Overall | ||
| CADD | 16.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.243%
African / African-American · 182/75,040 alleles
Filtering AF
0.214%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.203%
Overall
0.0133%
214/1,614,144 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.243% | 412 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0133% | 7,503 |
| South Asian | 0.0022% | 45,540 |
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
- CLDN1
- Protein
- p.Lys65=
- Coding
- c.195A>G
- MANE Select
- NM_021101
- dbSNP
- rs145197251
- Type
- single nucleotide variant
- Location
- chr3:190322012 (GRCh38)
- Gene constraint
- LOEUF 0.837 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.57
Similar variants
- CLDN1 p.Cys64Ter Pathogenic/Likely pathogenic ★★ same type
- CLDN1 p.Ala14Val Uncertain significance ★★ ⚠ same type
- CLDN1 p.Arg188Gln Uncertain significance ★★ ⚠ same type
- CLDN1 p.Leu165Val Uncertain significance ★★ ⚠ same type
- CLDN1 p.Pro202Leu Uncertain significance ★★ ⚠ same type
- CLDN1 p.Pro204Thr Uncertain significance ★★ ⚠ same type
- CLDN1 p.Val100Ile Uncertain significance ★★ ⚠ same type
- CLDN1 p.Val145Ile 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/cldn1-p-lys65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown