Is CHMP4B p.Ser150= (c.450G>A) pathogenic?

CHMP4B p.Ser150= (c.450G>A) is classified Benign in CHMP4B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). Rare (popmax 0.709%, mid); Associated with cataract 31 multiple types.

What condition is associated with CHMP4B p.Ser150= (c.450G>A)?

CHMP4B p.Ser150= (c.450G>A) is associated with cataract 31 multiple types (ClinVar).

How common is CHMP4B p.Ser150= (c.450G>A) in the general population?

CHMP4B p.Ser150= (c.450G>A) is rare (popmax 0.709%, mid) (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.Ser150=

c.450G>A · rs146262818 · VCV2190916

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.709%, mid)

Conditions

cataract 31 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP -4, phastCons 0.038
Overall
CADD	9.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.709% Middle Eastern · 43/6,062 alleles

Filtering AF 0.541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.482%

Overall 0.0448% 723/1,613,052 alleles · rare exomes 662/1,460,734 · genomes 61/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.709%	141
Ashkenazi Jewishnot grpmax-eligible	0.149%	673
Admixed American	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.064%	1,562
European (non-Finnish)	0.0439%	2,280
African / African-American	0.02%	5,002
South Asian	0.00988%	10,116
Finnishnot grpmax-eligible	0.00156%	64,036

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.Ser150=
Coding: c.450G>A
MANE Select: NM_176812
dbSNP: rs146262818
Type: single nucleotide variant
Location: chr20:33851033 (GRCh38)
Gene constraint: LOEUF 0.208 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB

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-ser150 (accessed [today's date]).

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