Is CHMP3 p.Asp152Glu (c.456C>A) pathogenic?

CHMP3 p.Asp152Glu (c.456C>A) is classified Uncertain significance in CHMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0245%, nfe).

How common is CHMP3 p.Asp152Glu (c.456C>A) in the general population?

CHMP3 p.Asp152Glu (c.456C>A) is ultra-rare (popmax 0.0245%, nfe) (gnomAD).

What do computational predictors say about CHMP3 p.Asp152Glu (c.456C>A)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CHMP3 p.Asp152Glu

c.456C>A · rs199633699 · VCV3144447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.8	GERP -5.6
Regional constraint	o/e 0.59	unconstrained · MANE · 22 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% European (non-Finnish) · 289/1,180,008 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0187% 302/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0245%	4,083
Remaining individualsnot grpmax-eligible	0.0112%	8,930
Finnishnot grpmax-eligible	0.00469%	21,333
African / African-American	0.004%	25,005

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: CHMP3
Protein: p.Asp152Glu
Coding: c.456C>A
MANE Select: NM_016079
dbSNP: rs199633699
Type: single nucleotide variant
Location: chr2:86507546 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 152: the 'interaction with vps4a' region; the 'intramolecular interaction with n-terminus' region

Full CHMP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP3 p.Ala52Val Uncertain significance ★ ⚠ same type
CHMP3 p.Arg39Thr Uncertain significance ★ ⚠ same type
CHMP3 p.Asp153Asn Uncertain significance ★ ⚠ same type
CHMP3 p.Glu14Lys Uncertain significance ★ ⚠ same type
CHMP3 p.Glu18Lys Uncertain significance ★ ⚠ same type
CHMP3 p.Ile23Met Uncertain significance ★ ⚠ same type
CHMP3 p.Lys10Glu Uncertain significance ★ ⚠ same type
CHMP3 p.Met84Val Uncertain significance ★ ⚠ 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/chmp3-p-asp152glu (accessed [today's date]).

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