CHRM2 p.Leu12=
c.34C>T · rs377626973 · VCV2845482
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00365%, nfe)
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 0.43 | GERP -0.68, phastCons 0.25 |
| Overall | ||
| CADD | 6.295 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00365%
European (non-Finnish) · 43/1,179,486 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00273%
44/1,613,036 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00365% | 27,430 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,408 |
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
- CHRM2
- Protein
- p.Leu12=
- Coding
- c.34C>T
- MANE Select
- NM_001006630
- dbSNP
- rs377626973
- Type
- single nucleotide variant
- Location
- chr7:137014899 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 72.87 · 17 PDB
Similar variants
- CHRM2 p.Ala265Val Uncertain significance ★★ ⚠ same type
- CHRM2 p.Arg52Cys Uncertain significance ★★ ⚠ same type
- CHRM2 p.Gln358His Uncertain significance ★★ ⚠ same type
- CHRM2 p.Glu305Gly Uncertain significance ★★ ⚠ same type
- CHRM2 p.Gly238Ala Uncertain significance ★★ ⚠ same type
- CHRM2 p.Gly254Val Uncertain significance ★★ ⚠ same type
- CHRM2 p.Gly277Glu Uncertain significance ★★ ⚠ same type
- CHRM2 p.Ile325Phe 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/chrm2-p-leu12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown