CHD2 p.Gln1392fs
c.4173dup · rs749969667 · VCV218395
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 33 of 39 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | A-rich low complexity · ambiguous alignment · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.431% | 232 |
| South Asian | 0.289% | 346 |
| European (non-Finnish) | 0.233% | 429 |
| East Asian | 0.231% | 434 |
| Ashkenazi Jewishnot grpmax-eligible | 0.22% | 455 |
| Remaining individualsnot grpmax-eligible | 0.176% | 567 |
| African / African-American | 0.155% | 644 |
| Finnishnot grpmax-eligible | 0.105% | 954 |
| Middle Eastern | 0.0887% | 1,127 |
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
- CHD2
- Protein
- p.Gln1392fs
- Coding
- c.4173dup
- MANE Select
- NM_001271
- dbSNP
- rs749969667
- Type
- Duplication
- Location
- chr15:93002203 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 1392
- a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region
Disease context
developmental and epileptic encephalopathy 94 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: complex neurodevelopmental disorder
For Lennox-Gastaut syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Multigenic/multifactorial, Not applicable
- Onset
- Childhood, Infancy
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- CHD2 p.Gln1392Ter Pathogenic ★ same residue
- CHD2 p.Gly1575_Lys1576insTer Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Tyr1246fs Pathogenic ★★ same condition
- CHD2 c.3595+18dup Benign/Likely benign ★★ same condition
- CHD2 c.4592+3_4592+5dup Likely benign ★★ same condition
- CHD2 p.Ala1024fs Likely pathogenic ★ same condition
- CHD2 p.Ala1330fs Pathogenic ★ same condition
- CHD2 p.Ala723fs 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/chd2-p-gln1392fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown