CNNM2 p.Ile435=
c.1305C>T · rs1355626818 · VCV2097470
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, 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 0.63 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 12.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,180,052 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,128 alleles · very rare
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
- CNNM2
- Protein
- p.Ile435=
- Coding
- c.1305C>T
- MANE Select
- NM_017649
- dbSNP
- rs1355626818
- Type
- single nucleotide variant
- Location
- chr10:102919785 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 7 PDB
- Residue 435
- an α-helix
Similar variants
- CNNM2 p.Ile435del Likely pathogenic ★ same residue
- CNNM2 p.Arg602Ter Likely pathogenic ★★ same type
- CNNM2 p.Asn327Ser Likely pathogenic ★★ same type
- CNNM2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ same type
- CNNM2 p.Glu357Lys Pathogenic ★★ same type
- CNNM2 p.Ser269Trp Pathogenic/Likely pathogenic ★★ same type
- CNNM2 c.1904-6C>G Uncertain significance ★★ same type
- CNNM2 p.Ala44Val 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/cnnm2-p-ile435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown