Is CHMP4B p.Asp129Val (c.386A>T) pathogenic?

CHMP4B p.Asp129Val (c.386A>T) is classified Pathogenic in CHMP4B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-09-01). AlphaMissense: likely pathogenic (0.9843); Absent from gnomAD v4.1; Associated with cataract 31 multiple types.

What condition is associated with CHMP4B p.Asp129Val (c.386A>T)?

CHMP4B p.Asp129Val (c.386A>T) is associated with cataract 31 multiple types (ClinVar).

How common is CHMP4B p.Asp129Val (c.386A>T) in the general population?

CHMP4B p.Asp129Val (c.386A>T) 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.Asp129Val (c.386A>T)?

AlphaMissense predicts likely pathogenic (score 0.9843) — an in-silico prediction, not a clinical call.

CHMP4B p.Asp129Val

c.386A>T · rs118203965 · VCV1085

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9843 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 31 multiple types

Computational evidence

Protein change
AlphaMissense	0.9843	likely pathogenic ✓ concordant with ClinVar
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -16.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 41 kb · p 2.1e-18 · regional, not allelic
Overall
CADD	33.0	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.Asp129Val
Coding: c.386A>T
MANE Select: NM_176812
dbSNP: rs118203965
Type: single nucleotide variant
Location: chr20:33850969 (GRCh38)
Gene constraint: LOEUF 0.208 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.98 · 4 PDB
Residue 129: 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.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-asp129val (accessed [today's date]).

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