CHAT p.Thr354=
c.1062G>A · rs529337162 · VCV530663
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.638%, sas)
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 -1.8 | GERP -4.6 |
| Overall | ||
| CADD | 4.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.638%
South Asian · 581/91,078 alleles
Filtering AF
0.595%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.578%
Overall
0.0407%
657/1,614,046 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.638% | 157 |
| Middle Eastern | 0.0495% | 2,019 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| Admixed American | 0.005% | 20,007 |
| East Asian | 0.00446% | 22,440 |
| African / African-American | 0.004% | 25,020 |
| European (non-Finnish) | 0.00347% | 28,779 |
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.Thr354=
- Coding
- c.1062G>A
- MANE Select
- NM_020549
- dbSNP
- rs529337162
- Type
- single nucleotide variant
- Location
- chr10:49627736 (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 354
- an α-helix
Similar variants
- CHAT p.Thr354Met Pathogenic/Likely pathogenic ★★ same residue
- CHAT p.Thr354Ser Likely pathogenic ★ ⚠ 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-thr354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown