CHRM3 p.Phe516=
c.1548T>C · rs1247175852 · VCV1972599
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
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 -0.5 | GERP -4.2, phastCons 0.074 |
| Overall | ||
| CADD | 4.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,078 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00031%
5/1,614,166 alleles · very rare
exomes 5/1,461,894 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,078 |
| European (non-Finnish) | 0.000339% | 295,008 |
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.Phe516=
- Coding
- c.1548T>C
- MANE Select
- NM_001375978
- dbSNP
- rs1247175852
- Type
- single nucleotide variant
- Location
- chr1:239908999 (GRCh38)
- Gene constraint
- LOEUF 0.42 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30 · 5 PDB
- Residue 516
- 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-phe516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown