CNNM4 p.Leu246=
c.738G>A · rs1199250960 · VCV2133641
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, 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 3.3 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 9.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,984 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000274%
4/1,457,938 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
- CNNM4
- Protein
- p.Leu246=
- Coding
- c.738G>A
- MANE Select
- NM_020184
- dbSNP
- rs1199250960
- Type
- single nucleotide variant
- Location
- chr2:96761737 (GRCh38)
- Gene constraint
- LOEUF 0.794 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.20 · 6 PDB
- Residue 246
- the cnnm transmembrane domain
Similar variants
- CNNM4 p.Arg519Ter Pathogenic ★★ same type
- CNNM4 p.Arg605Ter Pathogenic ★★ same type
- CNNM4 p.Gln564Ter Pathogenic ★★ same type
- CNNM4 p.Gln717Ter Pathogenic/Likely pathogenic ★★ same type
- CNNM4 c.2130+5G>A Uncertain significance ★★ same type
- CNNM4 c.*1126G>A Uncertain significance ★★ same type
- CNNM4 p.Ala297Gly Uncertain significance ★★ ⚠ same type
- CNNM4 p.Ala35Thr 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/cnnm4-p-leu246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown