Is CHMP3 p.Asp153Asn (c.457G>A) pathogenic?

CHMP3 p.Asp153Asn (c.457G>A) is classified Uncertain significance in CHMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely benign (0.1745); Ultra-rare (popmax 0.015%, amr).

How common is CHMP3 p.Asp153Asn (c.457G>A) in the general population?

CHMP3 p.Asp153Asn (c.457G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CHMP3 p.Asp153Asn (c.457G>A)?

AlphaMissense predicts likely benign (score 0.1745) — an in-silico prediction, not a clinical call.

CHMP3 p.Asp153Asn

c.457G>A · rs144721613 · VCV3144448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1745 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1745	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -10.68	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 22 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	29.6	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 0.015% Admixed American · 9/60,006 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00533% 86/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.008%	12,498
Finnishnot grpmax-eligible	0.00781%	12,804
European (non-Finnish)	0.00542%	18,438
East Asian	0.00223%	44,880
African / African-American	0.00133%	74,918
South Asian	0.0011%	91,080

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.Asp153Asn
Coding: c.457G>A
MANE Select: NM_016079
dbSNP: rs144721613
Type: single nucleotide variant
Location: chr2:86507545 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 153: 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.Asp152Glu 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-asp153asn (accessed [today's date]).

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