CHD2 p.Met1388fs
c.4164del · VCV4528312
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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 1.5 | GERP -0.018, phastCons 1 |
| 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.
Variant & gene context
- Gene
- CHD2
- Protein
- p.Met1388fs
- Coding
- c.4164del
- MANE Select
- NM_001271
- Type
- Deletion
- Location
- chr15:93002203 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 1388
- 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
Similar variants
- CHD2 p.Met1388Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- CHD2 p.Glu1412fs Pathogenic ★★ same type
- CHD2 p.Lys1393fs Pathogenic ★★ same type
- CHD2 p.Lys174_Val175insTer Pathogenic/Likely pathogenic ★★ same type
- CHD2 p.Pro399fs Pathogenic ★★ same type
- CHD2 c.1199-12del Benign/Likely benign ★★ same type
- CHD2 c.381+12del Likely benign ★★ same type
- CHD2 p.Lys1411del Benign/Likely benign ★★ 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/chd2-p-met1388fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown