Is CHMP2B p.Gln71His (c.213G>C) pathogenic?

CHMP2B p.Gln71His (c.213G>C) is classified Uncertain significance in CHMP2B (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-14). AlphaMissense: likely pathogenic (0.8733); Ultra-rare (popmax 0.032%, afr); Associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 7.

What condition is associated with CHMP2B p.Gln71His (c.213G>C)?

CHMP2B p.Gln71His (c.213G>C) is associated with frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (ClinVar).

How common is CHMP2B p.Gln71His (c.213G>C) in the general population?

CHMP2B p.Gln71His (c.213G>C) is ultra-rare (popmax 0.032%, afr) (gnomAD).

How is Behavioral variant of frontotemporal dementia inherited?

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

What do computational predictors say about CHMP2B p.Gln71His (c.213G>C)?

AlphaMissense predicts likely pathogenic (score 0.8733) — an in-silico prediction, not a clinical call.

CHMP2B p.Gln71His

c.213G>C · VCV3358842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Computational evidence

Protein change
AlphaMissense	0.8733	likely pathogenic
REVEL	0.639	indeterminate
SaProt	LLR -10.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.57, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.58 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/74,888 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00155% 25/1,613,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,120
Admixed American	0.00167%	59,980

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.Gln71His
Coding: c.213G>C
MANE Select: NM_014043
Type: single nucleotide variant
Location: chr3:87245800 (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-p-gln71his (accessed [today's date]).

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