Is CHMP7 p.Pro88Ala (c.262C>G) pathogenic?

CHMP7 p.Pro88Ala (c.262C>G) is classified Uncertain significance in CHMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely pathogenic (0.9285); Very rare (popmax 0.0024%, eas).

How common is CHMP7 p.Pro88Ala (c.262C>G) in the general population?

CHMP7 p.Pro88Ala (c.262C>G) is very rare (popmax 0.0024%, eas) (gnomAD).

What do computational predictors say about CHMP7 p.Pro88Ala (c.262C>G)?

AlphaMissense predicts likely pathogenic (score 0.9285) — an in-silico prediction, not a clinical call.

CHMP7 p.Pro88Ala

c.262C>G · VCV4002467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0024%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9285	likely pathogenic
REVEL	0.763	pathogenic-leaning
SaProt	LLR -12.39	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 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.075 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.0024% East Asian · 1/41,752 alleles

Overall 6.46e-05% 1/1,548,416 alleles · very rare exomes 1/1,396,098 · genomes 0/152,318 · joint denominator

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: CHMP7
Protein: p.Pro88Ala
Coding: c.262C>G
MANE Select: NM_152272
Type: single nucleotide variant
Location: chr8:23246957 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.53

Full CHMP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP7 p.Ala297= Benign ★★ same type
CHMP7 p.Leu347= Benign ★★ same type
CHMP7 p.Ala112Asp Uncertain significance ★ ⚠ same type
CHMP7 p.Ala12Gly Uncertain significance ★ ⚠ same type
CHMP7 p.Ala146Thr Uncertain significance ★ ⚠ same type
CHMP7 p.Ala160Gly Uncertain significance ★ ⚠ same type
CHMP7 p.Ala17Thr Uncertain significance ★ ⚠ same type
CHMP7 p.Ala188Val 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/chmp7-p-pro88ala (accessed [today's date]).

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