CHD2 p.Ser242Ter
c.725C>G · VCV4926673
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
CHD2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 8 of 39 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- CHD2
- Protein
- p.Ser242Ter
- Coding
- c.725C>G
- MANE Select
- NM_001271
- Type
- single nucleotide variant
- Location
- chr15:92941854 (GRCh38)
- Gene constraint
- LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.81
- Residue 242
- a modified residue (phosphoserine); 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
CHD2-related disorder
Similar variants
- CHD2 p.Arg1313Ter Pathogenic ★★ same condition
- CHD2 p.Arg1546Ter Pathogenic ★★ same condition
- CHD2 p.Arg224Ter Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Arg466Ter Pathogenic ★★ same condition
- CHD2 p.Gln1641Ter Pathogenic/Likely pathogenic ★★ same condition
- CHD2 p.Tyr1700Ter Pathogenic ★★ same condition
- CHD2 c.2352+1G>A Likely pathogenic ★ same condition
- CHD2 c.2506-1G>A Likely 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-ser242ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown