CHRM3 p.Pro173=
c.519G>A · VCV3710770
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -7.4 | GERP -4.2 |
| Overall | ||
| CADD | 2.437 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,890 alleles
Filtering AF
0.00639%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00592%
Overall
0.00682%
110/1,614,030 alleles · ultra-rare
exomes 103/1,461,892 · genomes 7/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,482 |
| European (non-Finnish) | 0.00771% | 12,967 |
| South Asian | 0.00769% | 13,012 |
| African / African-American | 0.00401% | 24,969 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
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.Pro173=
- Coding
- c.519G>A
- MANE Select
- NM_001375978
- Type
- single nucleotide variant
- Location
- chr1:239907970 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30 · 5 PDB
- Residue 173
- a turn
Similar variants
- 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
- CHRM3 p.Asn444Thr 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-pro173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown