CHAT p.Leu134=
c.400C>T · rs1438145765 · VCV2795612
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00879%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP -1.3, phastCons 1 |
| Overall | ||
| CADD | 7.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00879%
South Asian · 8/91,032 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.000496%
8/1,612,206 alleles · very rare
exomes 8/1,459,880 · genomes 0/152,326 · joint denominator
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.Leu134=
- Coding
- c.400C>T
- MANE Select
- NM_020549
- dbSNP
- rs1438145765
- Type
- single nucleotide variant
- Location
- chr10:49619737 (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 134
- 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-leu134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown