CHAT c.698+2T>C
Likely pathogenic
Multiple submitters
Classification
Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,607,894)
Conditions
2
congenital myasthenic syndrome 6
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.84 | donor loss · deltas |
| Pangolin | Δ0.79 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 2.4, phastCons 1 |
| Non-coding constraint | Z 2.23 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,607,894). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- CHAT
- Coding
- c.698+2T>C
- MANE Select
- NM_020549
- dbSNP
- rs904408037
- Type
- single nucleotide variant
- Location
- chr10:49620615 (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 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 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
- CHAT p.Arg281Trp 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-c-698-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown