CNNM4 p.Pro24=
c.72G>A · VCV4763516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0037%, amr)
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 6 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 14.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0037%
Admixed American · 1/27,042 alleles
Filtering AF
3.3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.2e-05%
Overall
0.000312%
4/1,284,072 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0037% | 27,042 |
| South Asian | 0.00338% | 29,564 |
| European (non-Finnish) | 0.000198% | 505,610 |
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.Pro24=
- Coding
- c.72G>A
- MANE Select
- NM_020184
- Type
- single nucleotide variant
- Location
- chr2:96761071 (GRCh38)
- Gene constraint
- LOEUF 0.794 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.20 · 6 PDB
Similar variants
- CNNM4 p.Pro24Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro24 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown