CHRM2 p.Asp252=
c.756C>T · rs531986911 · VCV1085441
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0184%, amr)
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 -7.9 | GERP -5.3 |
| Overall | ||
| CADD | 1.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0184%
Admixed American · 11/59,836 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00797%
Overall
0.00236%
38/1,612,972 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0184% | 5,440 |
| Middle Eastern | 0.0165% | 6,058 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,394 |
| African / African-American | 0.00801% | 12,489 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,614 |
| East Asian | 0.00224% | 44,602 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000848% | 117,954 |
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.Asp252=
- Coding
- c.756C>T
- MANE Select
- NM_001006630
- dbSNP
- rs531986911
- Type
- single nucleotide variant
- Location
- chr7:137015621 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 72.87 · 17 PDB
- Residue 252
- the 'disordered' region
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-asp252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown