CALM1 p.Phe142=
c.426C>T · rs199744595 · VCV1122289
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
3
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 0.68, phastCons 1 |
| Overall | ||
| CADD | 14.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,052 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.00112%
18/1,609,556 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,052 |
| African / African-American | 0.004% | 24,970 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,570 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,186 |
| East Asian | 0.00223% | 44,846 |
| South Asian | 0.0011% | 90,796 |
| European (non-Finnish) | 0.000765% | 130,679 |
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
- CALM1
- Protein
- p.Phe142=
- Coding
- c.426C>T
- MANE Select
- NM_006888
- dbSNP
- rs199744595
- Type
- single nucleotide variant
- Location
- chr14:90404693 (GRCh38)
- Gene constraint
- LOEUF 0.276 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.22 · 351 PDB
- Residue 142
- a UniProt-annotated variant site (in lqt14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; no effect on ryr2 interaction; significantly reduced ryanodine-sensitive calcium-release channel activity; impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential and); the ef-hand 4 domain; the 'necessary and sufficient for interaction with pcp4' region; an α-helix
Similar variants
- CALM1 p.Phe142Leu Pathogenic ★ same residue
- CALM1 p.Asn98Ser Pathogenic/Likely pathogenic ★★ same condition
- CALM1 p.Asp130Gly Pathogenic/Likely pathogenic ★★ same condition
- CALM1 c.4-3T>C Uncertain significance ★★ same condition
- CALM1 p.Arg87His Uncertain significance ★★ same condition
- CALM1 p.Glu120Lys Uncertain significance ★★ same condition
- CALM1 c.178+18A>G Benign/Likely benign ★★ same condition
- CALM1 c.179-4C>T Benign/Likely benign ★★ 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/calm1-p-phe142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown