CNNM2 p.Ala65=
c.195G>A · rs748005897 · VCV3052157
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0509%, mid)
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 3.7 | GERP -0.24, phastCons 1 |
| Overall | ||
| CADD | 10.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0509%
Middle Eastern · 3/5,896 alleles
Filtering AF
0.0358%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0318%
Overall
0.00367%
57/1,552,298 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0509% | 1,965 |
| South Asian | 0.0476% | 2,102 |
| Remaining individualsnot grpmax-eligible | 0.00665% | 15,035 |
| African / African-American | 0.00137% | 72,990 |
| European (non-Finnish) | 0.000784% | 127,612 |
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.Ala65=
- Coding
- c.195G>A
- MANE Select
- NM_017649
- dbSNP
- rs748005897
- Type
- single nucleotide variant
- Location
- chr10:102918675 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 7 PDB
Similar variants
- CNNM2 p.Ala65Val 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-ala65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown