CLDN14 p.Ser91=
c.273G>A · rs577393948 · VCV162969
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, 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 -9.9 | GERP -4.1 |
| Overall | ||
| CADD | 5.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,868 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00372%
60/1,613,222 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,639 |
| Admixed American | 0.0183% | 5,456 |
| Middle Eastern | 0.0165% | 6,060 |
| African / African-American | 0.00533% | 18,759 |
| European (non-Finnish) | 0.00212% | 47,199 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,496 |
| South Asian | 0.0011% | 91,080 |
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.Ser91=
- Coding
- c.273G>A
- MANE Select
- NM_001146079
- dbSNP
- rs577393948
- Type
- single nucleotide variant
- Location
- chr21:36461423 (GRCh38)
- Gene constraint
- LOEUF 1.745 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 80.00
Similar variants
- 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
- CLDN14 p.Ala98Thr Uncertain significance ★★ ⚠ same type
- CLDN14 p.Arg106Cys 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-ser91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown