CNNM4 p.Phe309=
c.927T>C · rs373657140 · VCV444511
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00636%, 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 -0.77 | GERP -3.2, phastCons 0.015 |
| Overall | ||
| CADD | 6.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00636%
European (non-Finnish) · 75/1,180,040 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00489%
79/1,614,050 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00636% | 15,734 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00167% | 59,996 |
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.Phe309=
- Coding
- c.927T>C
- MANE Select
- NM_020184
- dbSNP
- rs373657140
- Type
- single nucleotide variant
- Location
- chr2:96761926 (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 309
- 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-phe309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown