Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 12 submitters
gnomAD v4.1
Common
common (popmax 90.9%, nfe) — too common for a highly-penetrant pathogenic allele
Conditions
1
congenital myasthenic syndrome 6
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 -2.3 | GERP -4.4 |
| Overall | ||
| CADD | 0.974 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
90.9%
European (non-Finnish) · 1,072,234/1,179,906 alleles
Filtering AF
90.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 90.7%
Overall
88.2%
1,422,937/1,613,882 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 90.9% | 1 |
| Finnishnot grpmax-eligible | 89.1% | 1 |
| Remaining individualsnot grpmax-eligible | 87.3% | 1 |
| South Asian | 86.6% | 1 |
| Middle Eastern | 86.6% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 85.4% | 1 |
| Amishnot grpmax-eligible | 83.4% | 1 |
| East Asian | 78.6% | 1 |
| Admixed American | 70.6% | 1 |
| African / African-American | 68.5% | 1 |
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
- CHAT
- Protein
- p.His547=
- Coding
- c.1641T>C
- MANE Select
- NM_020549
- dbSNP
- rs8178992
- Type
- single nucleotide variant
- Location
- chr10:49655101 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.73 · 8 PDB
- Residue 547
- an α-helix
Similar variants
- CHAT c.1282-2A>T Likely pathogenic ★★ same condition
- CHAT c.1840-9A>G Pathogenic/Likely pathogenic ★★ same condition
- CHAT c.698+1G>T Likely pathogenic ★★ same condition
- CHAT c.698+2T>C Likely pathogenic ★★ same condition
- CHAT p.Ala557Thr Pathogenic/Likely pathogenic ★★ same condition
- CHAT p.Arg151Ter Pathogenic/Likely pathogenic ★★ same condition
- CHAT p.Arg207Gly Likely pathogenic ★★ same condition
- CHAT p.Arg207His Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/chat-p-his547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown