Is CHMP6 p.Leu52Pro (c.155T>C) pathogenic?

CHMP6 p.Leu52Pro (c.155T>C) is classified Uncertain significance in CHMP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely pathogenic (0.9794); Absent from gnomAD v4.1.

How common is CHMP6 p.Leu52Pro (c.155T>C) in the general population?

CHMP6 p.Leu52Pro (c.155T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHMP6 p.Leu52Pro (c.155T>C)?

AlphaMissense predicts likely pathogenic (score 0.9794) — an in-silico prediction, not a clinical call.

CHMP6 p.Leu52Pro

c.155T>C · VCV4002459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9794	likely pathogenic · top 3% in CHMP6
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -13.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,231 bp · p 0.75 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHMP6
Protein: p.Leu52Pro
Coding: c.155T>C
MANE Select: NM_024591
Type: single nucleotide variant
Location: chr17:80994672 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 82.51 · 2 PDB

Full CHMP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP6 p.Asn185= Benign ★★ same type
CHMP6 p.Gly55Ser Benign ★★ ⚠ same type
CHMP6 p.Ala190Asp Uncertain significance ★ ⚠ same type
CHMP6 p.Ala46Thr Uncertain significance ★ ⚠ same type
CHMP6 p.Arg12Pro Uncertain significance ★ ⚠ same type
CHMP6 p.Arg138Gln Uncertain significance ★ ⚠ same type
CHMP6 p.Arg45Cys Uncertain significance ★ ⚠ same type
CHMP6 p.Arg45His 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/chmp6-p-leu52pro (accessed [today's date]).

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