CHMP2B c.321+247del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 8.5%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +247 | deep intronic (+247 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -2.2 | GERP -0.34 |
| Non-coding constraint | Z -0.96 | 1 kb window · o/e 1.08 · regional · uncalibrated |
| Overall | ||
| CADD | 0.397 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5%
African / African-American · 3,422/40,272 alleles
Filtering AF
8.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.16%
Overall
2.51%
3,692/146,940 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.5% | 12 |
| Remaining individualsnot grpmax-eligible | 1.84% | 54 |
| Admixed American | 1.26% | 80 |
| Middle Eastern | 0.694% | 144 |
| Ashkenazi Jewishnot grpmax-eligible | 0.147% | 679 |
| European (non-Finnish) | 0.0572% | 1,747 |
| South Asian | 0.0433% | 2,309 |
| Finnishnot grpmax-eligible | 0.0317% | 3,153 |
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
- Coding
- c.321+247del
- MANE Select
- NM_014043
- dbSNP
- rs35848729
- Type
- Deletion
- Location
- chr3:87246146 (GRCh38)
- Gene constraint
- LOEUF 1.503 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.26 · 1 PDB
Similar variants
- CHMP2B p.Ala179fs Uncertain significance ★ same type
- CHMP2B p.Gln41fs Uncertain significance ★ same type
- CHMP2B p.Lys114fs Uncertain significance ★ same type
- CHMP2B c.127-273del Likely benign ★ same type
- CHMP2B c.322-299del Benign ★ same type
- CHMP2B c.424+19_424+21del 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/chmp2b-c-321-plus-247del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown