CLDN1 p.Ala124=
c.372G>A · rs545795665 · VCV2967737
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00533%, 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 -1.4 | GERP -2.1 |
| Overall | ||
| CADD | 9.572 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00533%
African / African-American · 4/75,020 alleles
Filtering AF
0.00174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000867%
14/1,614,068 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00533% | 18,755 |
| Admixed American | 0.00333% | 30,004 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000593% | 168,570 |
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.Ala124=
- Coding
- c.372G>A
- MANE Select
- NM_021101
- dbSNP
- rs545795665
- Type
- single nucleotide variant
- Location
- chr3:190312888 (GRCh38)
- Gene constraint
- LOEUF 0.837 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.57
Similar variants
- CLDN1 p.Ala124Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLDN1 p.Ala124Thr Likely benign ★ same residue
- 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
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-ala124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown