CDH2 p.Thr346=
c.1038G>A · rs140193518 · VCV1773219
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0055%, sas)
Conditions
1
Inborn genetic diseases
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 -12 | GERP -5.7 |
| Overall | ||
| CADD | 5.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0055%
South Asian · 5/90,976 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00137%
Overall
0.00174%
28/1,612,160 alleles · very rare
exomes 28/1,459,878 · genomes 0/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0055% | 18,195 |
| Admixed American | 0.00334% | 29,983 |
| European (non-Finnish) | 0.00178% | 56,113 |
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
- CDH2
- Protein
- p.Thr346=
- Coding
- c.1038G>A
- MANE Select
- NM_001792
- dbSNP
- rs140193518
- Type
- single nucleotide variant
- Location
- chr18:27993620 (GRCh38)
- Gene constraint
- LOEUF 0.336 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68
- Residue 346
- the cadherin 2 domain
Similar variants
- CDH2 p.Thr346Met Uncertain significance ★ ⚠ same residue
- CDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala294Gly Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala299Thr Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala415Ser Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala418Ser Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala418Thr Uncertain significance ★★ ⚠ same condition
- CDH2 p.Ala610Thr Uncertain significance ★★ ⚠ same condition
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/cdh2-p-thr346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown