Is CHMP7 p.Cys191Trp (c.573C>G) pathogenic?

CHMP7 p.Cys191Trp (c.573C>G) is classified Uncertain significance in CHMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.9106); Ultra-rare (popmax 0.0283%, amr).

How common is CHMP7 p.Cys191Trp (c.573C>G) in the general population?

CHMP7 p.Cys191Trp (c.573C>G) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

What do computational predictors say about CHMP7 p.Cys191Trp (c.573C>G)?

AlphaMissense predicts likely pathogenic (score 0.9106) — an in-silico prediction, not a clinical call.

CHMP7 p.Cys191Trp

c.573C>G · rs554721092 · VCV2221944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9106	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP 0.93, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.075 · regional, not allelic
Overall
CADD	23.4	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 0.0283% Admixed American · 17/60,028 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00142% 23/1,614,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,531
Remaining individualsnot grpmax-eligible	0.0064%	15,626
South Asian	0.0011%	91,080
European (non-Finnish)	8.47e-05%	1,180,030

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.Cys191Trp
Coding: c.573C>G
MANE Select: NM_152272
dbSNP: rs554721092
Type: single nucleotide variant
Location: chr8:23255348 (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-cys191trp (accessed [today's date]).

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