CHRM3 p.Ala495=
c.1485G>A · VCV4702417
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, 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 -0.6 | GERP -4.2, phastCons 0.007 |
| Overall | ||
| CADD | 8.077 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,900 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00105%
17/1,614,010 alleles · very rare
exomes 12/1,461,890 · genomes 5/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00935% | 10,700 |
| South Asian | 0.0022% | 45,546 |
| Admixed American | 0.00167% | 60,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
| European (non-Finnish) | 0.000424% | 236,008 |
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.Ala495=
- Coding
- c.1485G>A
- MANE Select
- NM_001375978
- Type
- single nucleotide variant
- Location
- chr1:239908936 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30 · 5 PDB
- Residue 495
- an α-helix
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-ala495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown