CNNM2 p.Glu487=
c.1461G>A · rs946949528 · VCV1955134
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
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 5.9 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 10.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,934 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00062%
10/1,614,124 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,326 |
| European (non-Finnish) | 8.47e-05% | 1,180,059 |
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.Glu487=
- Coding
- c.1461G>A
- MANE Select
- NM_017649
- dbSNP
- rs946949528
- Type
- single nucleotide variant
- Location
- chr10:102919941 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 7 PDB
- Residue 487
- the cbs 1 domain; a β-strand
Similar variants
- CNNM2 p.Glu487Asp Uncertain significance ★ 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-glu487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown