Is CHMP4B p.Glu90= (c.270G>A) pathogenic?

CHMP4B p.Glu90= (c.270G>A) is classified Benign in CHMP4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-23). Rare (popmax 0.619%, eas); Associated with cataract 31 multiple types.

What condition is associated with CHMP4B p.Glu90= (c.270G>A)?

CHMP4B p.Glu90= (c.270G>A) is associated with cataract 31 multiple types (ClinVar).

How common is CHMP4B p.Glu90= (c.270G>A) in the general population?

CHMP4B p.Glu90= (c.270G>A) is rare (popmax 0.619%, eas) (gnomAD).

How is Early onset non-syndromic cataract inherited?

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

CHMP4B p.Glu90=

c.270G>A · rs77820932 · VCV2188536

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.619%, eas)

Conditions

cataract 31 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.91, phastCons 1
Overall
CADD	12.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.619% East Asian · 278/44,878 alleles

Filtering AF 0.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.536%

Overall 0.0189% 305/1,614,222 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.619%	161
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.00439%	22,772
Admixed American	0.00167%	60,034

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: CHMP4B
Protein: p.Glu90=
Coding: c.270G>A
MANE Select: NM_176812
dbSNP: rs77820932
Type: single nucleotide variant
Location: chr20:33848546 (GRCh38)
Gene constraint: LOEUF 0.208 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB
Residue 90: an α-helix

Full CHMP4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 31 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CHMP4B p.Gly154Arg Uncertain significance ★★ ⚠ same condition
CHMP4B c.191-5C>T Benign/Likely benign ★★ same condition
CHMP4B p.Pro186= Benign/Likely benign ★★ same condition
CHMP4B p.Gln67Arg Likely pathogenic ★ same condition
CHMP4B p.Glu104Lys Uncertain significance ★ ⚠ same condition
CHMP4B p.Glu161Gln Uncertain significance ★ ⚠ same condition
CHMP4B p.Ser196Ala Uncertain significance ★ ⚠ same condition
CHMP4B c.368+15G>A Likely benign ★ 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/chmp4b-p-glu90 (accessed [today's date]).

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