Is CHMP2B c.321+10A>C pathogenic?

CHMP2B c.321+10A>C is classified Likely benign in CHMP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). Ultra-rare (popmax 0.0255%, afr); Associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 7.

What condition is associated with CHMP2B c.321+10A>C?

CHMP2B c.321+10A>C is associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (ClinVar).

How common is CHMP2B c.321+10A>C in the general population?

CHMP2B c.321+10A>C is ultra-rare (popmax 0.0255%, afr) (gnomAD).

How is Behavioral variant of frontotemporal dementia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHMP2B c.321+10A>C

rs371149284 · VCV2077387

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, afr)

Conditions

frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +10	near-intronic (+10 nt from the splice site)
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.33	GERP -4.5
Overall
CADD	5.854	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0255% African / African-American · 19/74,500 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00145% 23/1,590,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0255%	3,921
Admixed American	0.00336%	29,722
Remaining individualsnot grpmax-eligible	0.00162%	61,684
European (non-Finnish)	8.61e-05%	1,161,170

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+10A>C
MANE Select: NM_014043
dbSNP: rs371149284
Type: single nucleotide variant
Location: chr3:87245918 (GRCh38)
Gene constraint: LOEUF 1.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.26 · 1 PDB

Full CHMP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

frontotemporal dementia and/or amyotrophic lateral sclerosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Behavioral variant of frontotemporal dementia (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: 1-9 / 100 000 (Netherlands)

Similar variants

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
CHMP2B p.Ile29Val 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-c-321-plus-10a-c (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown