CHRM2 p.Thr446=
c.1338C>T · rs763752437 · VCV1128154
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 1.4 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 8.586 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,812 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.00093%
15/1,612,932 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,406 |
| European (non-Finnish) | 0.0011% | 90,720 |
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.Thr446=
- Coding
- c.1338C>T
- MANE Select
- NM_001006630
- dbSNP
- rs763752437
- Type
- single nucleotide variant
- Location
- chr7:137016203 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 72.87 · 17 PDB
- Residue 446
- a modified residue (phosphothreonine); an α-helix
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-thr446 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown