CHAT c.579+240T>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.35%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +240 | deep intronic (+240 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -3.4 |
| Non-coding constraint | Z 2.23 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 0.027 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.35%
African / African-American · 959/40,756 alleles
Filtering AF
2.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.18%
Overall
0.715%
1,074/150,120 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.35% | 42 |
| Ashkenazi Jewishnot grpmax-eligible | 1.76% | 57 |
| Middle Eastern | 1.03% | 97 |
| Remaining individualsnot grpmax-eligible | 0.431% | 232 |
| Admixed American | 0.205% | 487 |
| European (non-Finnish) | 0.0163% | 6,138 |
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.579+240T>A
- MANE Select
- NM_020549
- dbSNP
- rs114414580
- Type
- single nucleotide variant
- Location
- chr10:49620156 (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-579-plus-240t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown