CNNM2 p.Ser708=
c.2124C>T · VCV3714543
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 -6.6 | GERP -5.7 |
| Overall | ||
| CADD | 5.669 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/74,892 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00989%
Overall
0.00174%
28/1,613,010 alleles · ultra-rare
exomes 17/1,460,826 · genomes 11/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 4,993 |
| Middle Eastern | 0.0164% | 6,084 |
| East Asian | 0.00446% | 22,430 |
| Admixed American | 0.00167% | 59,922 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,438 |
| South Asian | 0.0011% | 90,740 |
| European (non-Finnish) | 0.000593% | 168,514 |
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.Ser708=
- Coding
- c.2124C>T
- MANE Select
- NM_017649
- Type
- single nucleotide variant
- Location
- chr10:103068679 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 7 PDB
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-ser708 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown