CNNM2 p.Leu415=
c.1243C>T · rs113308552 · VCV1553079
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0613%, 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 2.8 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 13.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0613%
African / African-American · 46/75,058 alleles
Filtering AF
0.0471%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0422%
Overall
0.00434%
70/1,614,214 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0613% | 1,632 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00333% | 30,016 |
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.Leu415=
- Coding
- c.1243C>T
- MANE Select
- NM_017649
- dbSNP
- rs113308552
- Type
- single nucleotide variant
- Location
- chr10:102919723 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 7 PDB
- Residue 415
- the cnnm transmembrane domain
Similar variants
- 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
- CNNM2 p.Ala45Glu 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-leu415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown