Is CHMP4B p.Glu161Gln (c.481G>C) pathogenic?

CHMP4B p.Glu161Gln (c.481G>C) is classified Uncertain significance in CHMP4B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-21). AlphaMissense: likely pathogenic (0.8758); Absent from gnomAD v4.1; Associated with cataract 31 multiple types.

What condition is associated with CHMP4B p.Glu161Gln (c.481G>C)?

CHMP4B p.Glu161Gln (c.481G>C) is associated with cataract 31 multiple types (ClinVar).

How common is CHMP4B p.Glu161Gln (c.481G>C) in the general population?

CHMP4B p.Glu161Gln (c.481G>C) is absent from gnomAD v4.1 (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.

What do computational predictors say about CHMP4B p.Glu161Gln (c.481G>C)?

AlphaMissense predicts likely pathogenic (score 0.8758) — an in-silico prediction, not a clinical call.

CHMP4B p.Glu161Gln

c.481G>C · rs118203966 · VCV1473882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 31 multiple types

Computational evidence

Protein change
AlphaMissense	0.8758	likely pathogenic
REVEL	0.637	indeterminate
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 41 kb · p 2.1e-18 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHMP4B
Protein: p.Glu161Gln
Coding: c.481G>C
MANE Select: NM_176812
dbSNP: rs118203966
Type: single nucleotide variant
Location: chr20:33851064 (GRCh38)
Gene constraint: LOEUF 0.208 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB
Residue 161: a UniProt-annotated variant site (in ctrct31)

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.Glu161Lys Pathogenic same residue
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.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-glu161gln (accessed [today's date]).

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