CHAT c.286+5G>A
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +5 | donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.20 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 26.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Amishnot grpmax-eligible | 0.989% | 101 |
| South Asiangrpmax | 0.00238% | 41,985 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,792 |
| European (non-Finnish) | 0.000262% | 382,037 |
Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- Coding
- c.286+5G>A
- MANE Select
- NM_020549
- Type
- single nucleotide variant
- Location
- chr10:49614480 (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 type
- CHAT c.1840-9A>G Pathogenic/Likely pathogenic ★★ same type
- CHAT c.698+1G>T Likely pathogenic ★★ same type
- CHAT c.698+2T>C Likely pathogenic ★★ same type
- CHAT p.Ala557Thr Pathogenic/Likely pathogenic ★★ same type
- CHAT p.Arg151Ter Pathogenic/Likely pathogenic ★★ same type
- CHAT p.Arg207Gly Likely pathogenic ★★ same type
- CHAT p.Arg207His Pathogenic/Likely pathogenic ★★ ⚠ same type
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-286-plus-5g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown