Is CHMP5 p.Asp159Glu (c.477T>G) pathogenic?

CHMP5 p.Asp159Glu (c.477T>G) is classified Uncertain significance in CHMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely pathogenic (0.7031); Very rare (popmax 8.54e-05%, nfe).

How common is CHMP5 p.Asp159Glu (c.477T>G) in the general population?

CHMP5 p.Asp159Glu (c.477T>G) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about CHMP5 p.Asp159Glu (c.477T>G)?

AlphaMissense predicts likely pathogenic (score 0.7031) — an in-silico prediction, not a clinical call.

CHMP5 p.Asp159Glu

c.477T>G · VCV3833083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7031	likely pathogenic
REVEL	0.755	pathogenic-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.31	GERP 0.79, phastCons 0.41
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 0.0049 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,170,406 alleles

Overall 6.9e-05% 1/1,450,262 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: CHMP5
Protein: p.Asp159Glu
Coding: c.477T>G
MANE Select: NM_016410
Type: single nucleotide variant
Location: chr9:33276545 (GRCh38)
Gene constraint: LOEUF 1.441 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 6 PDB

Full CHMP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP5 p.Ala186Thr Uncertain significance ★ ⚠ same type
CHMP5 p.Ala191Val Uncertain significance ★ ⚠ same type
CHMP5 p.Arg79Gln Uncertain significance ★ ⚠ same type
CHMP5 p.Arg79Trp Uncertain significance ★ ⚠ same type
CHMP5 p.Asn143Ser Uncertain significance ★ ⚠ same type
CHMP5 p.Asn81Asp Uncertain significance ★ ⚠ same type
CHMP5 p.Asp25Glu Uncertain significance ★ ⚠ same type
CHMP5 p.Asp39Ala 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/chmp5-p-asp159glu (accessed [today's date]).

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