Is CHMP4B p.Val153Ala (c.458T>C) pathogenic?

CHMP4B p.Val153Ala (c.458T>C) is classified Uncertain significance in CHMP4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: ambiguous (0.3486); Very rare (popmax 0.00401%, afr).

How common is CHMP4B p.Val153Ala (c.458T>C) in the general population?

CHMP4B p.Val153Ala (c.458T>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CHMP4B p.Val153Ala (c.458T>C)?

AlphaMissense predicts ambiguous (score 0.3486) — an in-silico prediction, not a clinical call.

CHMP4B p.Val153Ala

c.458T>C · rs1979832268 · VCV2472426

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
AlphaMissense	0.3486	ambiguous
REVEL	0.439	indeterminate
SaProt	LLR -7.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 41 kb · p 2.1e-18 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00401% African / African-American · 3/74,862 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,610,858 alleles · very rare

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.Val153Ala
Coding: c.458T>C
MANE Select: NM_176812
dbSNP: rs1979832268
Type: single nucleotide variant
Location: chr20:33851041 (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

Similar variants

CHMP4B p.Gly154Arg Uncertain significance ★★ ⚠ same type
CHMP4B c.190+226C>G Benign ★★ same type
CHMP4B c.191-5C>T Benign/Likely benign ★★ same type
CHMP4B c.610+159T>C Benign ★★ same type
CHMP4B c.610+44A>G Benign ★★ same type
CHMP4B c.610+51C>G Benign ★★ same type
CHMP4B c.610+52T>C Benign ★★ same type
CHMP4B c.610+81G>A Likely benign ★★ same type

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-val153ala (accessed [today's date]).

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