CLDN16 p.Ala209=
c.627C>T · rs745542693 · VCV1573821
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -3.5 | GERP -5.4 |
| Overall | ||
| CADD | 0.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,864 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000547%
8/1,461,704 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,864 |
| European (non-Finnish) | 0.000593% | 168,553 |
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
- CLDN16
- Protein
- p.Ala209=
- Coding
- c.627C>T
- MANE Select
- NM_006580
- dbSNP
- rs745542693
- Type
- single nucleotide variant
- Location
- chr3:190409955 (GRCh38)
- Gene constraint
- LOEUF 0.837 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74
- Residue 209
- a UniProt-annotated variant site (in homg3; retained in the endoplasmic reticulum and targeted for proteasomal degradation); a UniProt-annotated variant site (in homg3; retained intracellularly with predominant localization in the golgi apparatus and further targeted to lysosomes)
Similar variants
- CLDN16 p.Ala209Asp Benign/Likely benign ★★ same residue
- CLDN16 c.217+1G>A Likely pathogenic ★★ same type
- CLDN16 c.217+5G>A Pathogenic/Likely pathogenic ★★ same type
- CLDN16 p.Arg146Cys Pathogenic/Likely pathogenic ★★ same type
- CLDN16 p.Arg146His Pathogenic/Likely pathogenic ★★ ⚠ same type
- CLDN16 p.Arg44Ter Pathogenic/Likely pathogenic ★★ same type
- CLDN16 p.Arg79Ter Pathogenic ★★ same type
- CLDN16 p.Asp35Asn Likely pathogenic ★★ 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/cldn16-p-ala209 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown