CHMP2B p.Arg22Ter
c.64C>T · rs138886714 · VCV704339
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 |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 6 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 39.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.585% | 171 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,402 |
| European (non-Finnish)grpmax | 0.00382% | 26,207 |
| East Asian | 0.00223% | 44,840 |
| Admixed American | 0.00167% | 59,968 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- CHMP2B
- Protein
- p.Arg22Ter
- Coding
- c.64C>T
- MANE Select
- NM_014043
- dbSNP
- rs138886714
- Type
- single nucleotide variant
- Location
- chr3:87240728 (GRCh38)
- Gene constraint
- LOEUF 1.503 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.26 · 1 PDB
Disease context
frontotemporal dementia and/or amyotrophic lateral sclerosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Behavioral variant of frontotemporal dementia (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Adult
- Prevalence
- 1-9 / 100 000 (Netherlands)
Similar variants
- CHMP2B p.Arg22Gln Uncertain significance ★ ⚠ same residue
- CHMP2B c.126+4A>G Uncertain significance ★★ same condition
- CHMP2B p.Arg205Gln Uncertain significance ★★ ⚠ same condition
- CHMP2B p.Arg205Leu Uncertain significance ★★ ⚠ same condition
- CHMP2B p.Arg205Trp Uncertain significance ★★ same condition
- CHMP2B p.Arg69Trp Uncertain significance ★★ ⚠ same condition
- CHMP2B p.Asn113Lys Uncertain significance ★★ ⚠ same condition
- CHMP2B p.Asn143Ser 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/chmp2b-p-arg22ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown