CHAT p.Pro299=
c.897G>A · rs756942813 · VCV1661029
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0068%, eas)
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 -20 | GERP -4.7 |
| Overall | ||
| CADD | 0.066 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0068%
East Asian · 3/44,146 alleles
Filtering AF
0.0018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00138%
22/1,593,908 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0068% | 14,715 |
| African / African-American | 0.00536% | 18,640 |
| South Asian | 0.00454% | 22,035 |
| Admixed American | 0.00175% | 57,008 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,742 |
| Finnishnot grpmax-eligible | 0.0016% | 62,608 |
| European (non-Finnish) | 0.000684% | 146,200 |
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.Pro299=
- Coding
- c.897G>A
- MANE Select
- NM_020549
- dbSNP
- rs756942813
- Type
- single nucleotide variant
- Location
- chr10:49625617 (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 299
- a UniProt-annotated variant site (in)
Similar variants
- CHAT p.Pro299Leu Benign/Likely benign ★★ same residue
- CHAT p.Pro299Ser Uncertain significance ★ same residue
- 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
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-pro299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown