CHAT c.1111+45G>A
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 14.5%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +45 | near-intronic (+45 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -4.3, phastCons 0.7 |
| Overall | ||
| CADD | 1.828 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
14.5%
African / African-American · 10,828/74,684 alleles
Filtering AF
14.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.2%
Overall
0.832%
13,263/1,593,994 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 14.5% | 7 |
| Remaining individualsnot grpmax-eligible | 1.25% | 80 |
| Admixed American | 1.14% | 87 |
| Middle Eastern | 1.14% | 88 |
| Ashkenazi Jewishnot grpmax-eligible | 0.102% | 981 |
| South Asian | 0.0957% | 1,045 |
| European (non-Finnish) | 0.0696% | 1,436 |
| East Asian | 0.00225% | 44,402 |
| Finnishnot grpmax-eligible | 0.00175% | 57,086 |
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.1111+45G>A
- MANE Select
- NM_020549
- dbSNP
- rs58788269
- Type
- single nucleotide variant
- Location
- chr10:49627830 (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-1111-plus-45g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown