CNTN2 p.Val565=
c.1695G>A · rs148801784 · VCV474466
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.152%, nfe)
Conditions
2
epilepsy, familial adult myoclonic, 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.43 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.63 | loss · gain 0.23 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.6 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 22.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.152%
European (non-Finnish) · 1,794/1,180,012 alleles
Filtering AF
0.146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.144%
Overall
0.117%
1,894/1,613,956 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.152% | 658 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| Finnishnot grpmax-eligible | 0.0453% | 2,208 |
| African / African-American | 0.0187% | 5,349 |
| Middle Eastern | 0.0164% | 6,084 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Admixed American | 0.00167% | 59,988 |
| South Asian | 0.0011% | 91,072 |
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
- CNTN2
- Protein
- p.Val565=
- Coding
- c.1695G>A
- MANE Select
- NM_005076
- dbSNP
- rs148801784
- Type
- single nucleotide variant
- Location
- chr1:205065262 (GRCh38)
- Gene constraint
- LOEUF 0.542 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 86.13 · 5 PDB
- Residue 565
- the ig-like c2-type 6 domain
Similar variants
- CNTN2 p.Val565Met Uncertain significance ★ ⚠ same residue
- CNTN2 c.1241-1G>C Likely pathogenic ★★ same condition
- CNTN2 c.2432-2A>G Likely pathogenic ★★ same condition
- CNTN2 p.Arg140Ter Pathogenic/Likely pathogenic ★★ same condition
- CNTN2 p.Arg314Ter Pathogenic ★★ same condition
- CNTN2 p.Trp731Ter Pathogenic/Likely pathogenic ★★ same condition
- CNTN2 c.2196+5G>A Uncertain significance ★★ same condition
- CNTN2 p.Ala230Val 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/cntn2-p-val565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown