CHAT p.Pro138=
c.414G>A · rs199675090 · VCV1541703
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0177%, mid)
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 | all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.2 | GERP -4.1 |
| Overall | ||
| CADD | 0.132 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0177%
Middle Eastern · 1/5,652 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00124%
20/1,613,048 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0177% | 5,652 |
| East Asian | 0.00891% | 11,225 |
| African / African-American | 0.00401% | 24,965 |
| Admixed American | 0.00167% | 59,986 |
| South Asian | 0.0011% | 91,040 |
| European (non-Finnish) | 0.000847% | 117,999 |
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.Pro138=
- Coding
- c.414G>A
- MANE Select
- NM_020549
- dbSNP
- rs199675090
- Type
- single nucleotide variant
- Location
- chr10:49619751 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.73 · 8 PDB
Similar variants
- CHAT p.Pro138Gln Uncertain significance ★ ⚠ same residue
- CHAT p.Pro138Leu Uncertain significance ★ ⚠ same residue
- CHAT p.Pro138fs 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
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-pro138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown