CHAT p.Glu629Lys
c.1885G>A · VCV3383391
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5279 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5279 | ambiguous |
|---|---|---|
| REVEL | 0.783 | moderately pathogenic-leaning |
| SaProt | LLR -9.50 | tolerated |
| ⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic |
| Overall | ||
| CADD | 26.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CHAT
- Protein
- p.Glu629Lys
- Coding
- c.1885G>A
- MANE Select
- NM_020549
- Type
- single nucleotide variant
- Location
- chr10:49662690 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.73 · 8 PDB
- Residue 629
- an α-helix
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-p-glu629lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown