CALM2 p.Arg107Cys
c.319C>T · rs1312868284 · VCV956093
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.925 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.21 | constrained · MANE · 16 kb · p 6.7e-26 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,368 alleles
Overall
6.85e-05%
1/1,460,648 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
- CALM2
- Protein
- p.Arg107Cys
- Coding
- c.319C>T
- MANE Select
- NM_001743
- dbSNP
- rs1312868284
- Type
- single nucleotide variant
- Location
- chr2:47161825 (GRCh38)
- Gene constraint
- LOEUF 0.262 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.82 · 21 PDB
- Residue 107
- the ef-hand 3 domain; the 'necessary and sufficient for interaction with pcp4' region; an α-helix
Similar variants
- CALM2 p.Asn98Ser Pathogenic ★★ same condition
- CALM2 p.Asp134Asn Likely pathogenic ★★ same condition
- CALM2 p.Asp96Tyr Pathogenic/Likely pathogenic ★★ same condition
- CALM2 p.Asp96Val Pathogenic ★★ same condition
- CALM2 c.285+5G>A Uncertain significance ★★ same condition
- CALM2 c.-2G>C Uncertain significance ★★ same condition
- CALM2 c.-4C>T Uncertain significance ★★ same condition
- CALM2 p.Ala58Pro Uncertain significance ★★ same condition
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/calm2-p-arg107cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown