CALM2 p.Ala58Pro
c.172G>C · rs2103825594 · VCV1305058
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
long QT syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.815 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.21 | constrained · MANE · 16 kb · p 6.7e-26 · regional, not allelic |
| Overall | ||
| CADD | 29.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CALM2
- Protein
- p.Ala58Pro
- Coding
- c.172G>C
- MANE Select
- NM_001743
- dbSNP
- rs2103825594
- Type
- single nucleotide variant
- Location
- chr2:47162525 (GRCh38)
- Gene constraint
- LOEUF 0.262 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.82 · 21 PDB
- Residue 58
- the ef-hand 2 domain; a β-strand
Disease context
long QT syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Romano-Ward syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-5 / 10 000 (Europe)
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 p.Arg107Cys Uncertain significance ★★ same condition
- CALM2 p.Arg91Cys Uncertain significance ★★ same condition
- CALM2 p.Glu140= 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-ala58pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown