CADM3 p.Pro65=
c.195T>G · rs140248716 · VCV2639483
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0866%, nfe)
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 0.69 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 11.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0866%
European (non-Finnish) · 1,022/1,180,014 alleles
Filtering AF
0.0822%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0804%
Overall
0.0687%
1,109/1,614,134 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0866% | 1,155 |
| Remaining individualsnot grpmax-eligible | 0.0512% | 1,953 |
| Admixed American | 0.045% | 2,223 |
| Finnishnot grpmax-eligible | 0.0328% | 3,047 |
| African / African-American | 0.00933% | 10,722 |
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
- CADM3
- Protein
- p.Pro65=
- Coding
- c.195T>G
- MANE Select
- NM_001127173
- dbSNP
- rs140248716
- Type
- single nucleotide variant
- Location
- chr1:159192042 (GRCh38)
- Gene constraint
- LOEUF 0.381 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.97 · 1 PDB
- Residue 65
- a disulfide bond; the ig-like v-type domain
Similar variants
- CADM3 p.Tyr138Cys Likely pathogenic ★★ ⚠ same type
- CADM3 c.89-2102C>T Uncertain significance ★★ same type
- CADM3 p.Leu13Gln Uncertain significance ★★ ⚠ same type
- CADM3 p.Tyr354Cys Uncertain significance ★★ ⚠ same type
- CADM3 c.229+11A>G Uncertain significance ★ same type
- CADM3 c.382+1G>A Uncertain significance ★ same type
- CADM3 c.89-2118G>A Uncertain significance ★ same type
- CADM3 c.89-2133A>T 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/cadm3-p-pro65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown