Is CHMP3 p.Met84Val (c.250A>G) pathogenic?

CHMP3 p.Met84Val (c.250A>G) is classified Uncertain significance in CHMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: ambiguous (0.3995); Very rare (popmax 0.000254%, nfe).

How common is CHMP3 p.Met84Val (c.250A>G) in the general population?

CHMP3 p.Met84Val (c.250A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CHMP3 p.Met84Val (c.250A>G)?

AlphaMissense predicts ambiguous (score 0.3995) — an in-silico prediction, not a clinical call.

CHMP3 p.Met84Val

c.250A>G · rs752418529 · VCV3144446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3995	ambiguous
REVEL	0.407	indeterminate
SaProt	LLR -14.06	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 22 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	22.4	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 0.000254% European (non-Finnish) · 3/1,179,318 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,459,994 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: CHMP3
Protein: p.Met84Val
Coding: c.250A>G
MANE Select: NM_016079
dbSNP: rs752418529
Type: single nucleotide variant
Location: chr2:86529254 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 84: the 'intramolecular interaction with c-terminus' region; an α-helix

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.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

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-met84val (accessed [today's date]).

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