CHD3 p.Phe1374fs
c.4120_4121del · VCV4933431
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
CHD3-related disorders
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 LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 26 of 40 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.88, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CHD3
- Protein
- p.Phe1374fs
- Coding
- c.4120_4121del
- MANE Select
- NM_001005273
- Type
- Deletion
- Location
- chr17:7905147 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.21
- Residue 1374
- the 'disordered' region; a UniProt-annotated variant site (in snibcps)
Disease context
CHD3-related disorders
Similar variants
- CHD3 p.Lys1044fs Likely pathogenic ★ same condition
- CHD3 c.4357_4358+2del Conflicting classifications of pathogenicity ★ ⚠ same condition
- CHD3 p.Lys1345fs Likely pathogenic same condition
- CHD3 p.Ser1156_Asp1157del Likely pathogenic same condition
- CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
- CHD3 p.Arg1342Gln Pathogenic/Likely pathogenic ★★ same condition
- CHD3 p.Arg985Gln Pathogenic ★★ same condition
- CHD3 p.Arg1491His Uncertain significance ★★ ⚠ 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/chd3-p-phe1374fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown