CHRM3 p.Asp353=
c.1059C>T · rs139009806 · VCV708305
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.257%, 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 -9.8 | GERP -4.2 |
| Overall | ||
| CADD | 1.444 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.257%
Admixed American · 149/58,044 alleles
Filtering AF
0.223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.21%
Overall
0.161%
2,576/1,598,936 alleles · rare
exomes 2,392/1,446,692 · genomes 184/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.257% | 390 |
| Amishnot grpmax-eligible | 0.22% | 455 |
| European (non-Finnish) | 0.195% | 514 |
| Remaining individualsnot grpmax-eligible | 0.167% | 600 |
| Middle Eastern | 0.0335% | 2,988 |
| African / African-American | 0.0296% | 3,384 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0245% | 4,080 |
| Finnishnot grpmax-eligible | 0.0111% | 9,022 |
| South Asian | 0.00225% | 44,501 |
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
- CHRM3
- Protein
- p.Asp353=
- Coding
- c.1059C>T
- MANE Select
- NM_001375978
- dbSNP
- rs139009806
- Type
- single nucleotide variant
- Location
- chr1:239908510 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30 · 5 PDB
- Residue 353
- the 'disordered' region
Similar variants
- CHRM3 p.Asp353Asn Uncertain significance ★★ ⚠ same residue
- CHRM3 p.Ala585Thr Uncertain significance ★★ ⚠ same type
- CHRM3 p.Ala589Asp Uncertain significance ★★ ⚠ same type
- CHRM3 p.Arg310His Uncertain significance ★★ ⚠ same type
- CHRM3 p.Arg44Gln Uncertain significance ★★ ⚠ same type
- CHRM3 p.Arg569Cys Uncertain significance ★★ ⚠ same type
- CHRM3 p.Arg584His Uncertain significance ★★ ⚠ same type
- CHRM3 p.Asn339Lys 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/chrm3-p-asp353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown