CALM3 p.Pro67=
c.201G>A · rs34089805 · VCV240117
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Rare
rare (popmax 0.492%, nfe)
Conditions
2
Cardiovascular phenotype
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 -5 | GERP -3.7 |
| Overall | ||
| CADD | 13.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.492%
European (non-Finnish) · 5,806/1,179,918 alleles
Filtering AF
0.481%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.477%
Overall
0.389%
6,277/1,614,060 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.492% | 203 |
| Remaining individualsnot grpmax-eligible | 0.373% | 268 |
| Admixed American | 0.185% | 541 |
| African / African-American | 0.0733% | 1,364 |
| Finnishnot grpmax-eligible | 0.0718% | 1,392 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0507% | 1,974 |
| Middle Eastern | 0.0495% | 2,021 |
| East Asian | 0.0156% | 6,411 |
| South Asian | 0.0011% | 91,084 |
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
- CALM3
- Protein
- p.Pro67=
- Coding
- c.201G>A
- MANE Select
- NM_005184
- dbSNP
- rs34089805
- Type
- single nucleotide variant
- Location
- chr19:46608504 (GRCh38)
- Gene constraint
- LOEUF 0.556 · pLI 0.93 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.45 · 26 PDB
- Residue 67
- the ef-hand 2 domain; an α-helix
Similar variants
- CALM3 p.Asp94Ala Pathogenic/Likely pathogenic ★★ same condition
- CALM3 p.Asp96His Pathogenic/Likely pathogenic ★★ same condition
- CALM3 p.Glu141Lys Pathogenic ★★ same condition
- CALM3 c.34+3G>A Uncertain significance ★★ same condition
- CALM3 c.421+5G>A Uncertain significance ★★ same condition
- CALM3 p.Ala148Thr Uncertain significance ★★ ⚠ same condition
- CALM3 p.Arg107Cys Uncertain significance ★★ ⚠ same condition
- CALM3 p.Asp132Asn 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/calm3-p-pro67 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown