Is CHMP6 p.Ala190Asp (c.569C>A) pathogenic?

CHMP6 p.Ala190Asp (c.569C>A) is classified Uncertain significance in CHMP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.0859); Rare (popmax 0.288%, afr).

How common is CHMP6 p.Ala190Asp (c.569C>A) in the general population?

CHMP6 p.Ala190Asp (c.569C>A) is rare (popmax 0.288%, afr) (gnomAD).

What do computational predictors say about CHMP6 p.Ala190Asp (c.569C>A)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

CHMP6 p.Ala190Asp

c.569C>A · rs149377306 · VCV2355860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.288%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.1, phastCons 0.65
Regional constraint	o/e 1.02	unconstrained · MANE · 7,231 bp · p 0.75 · regional, not allelic
Overall
CADD	11.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.288% African / African-American · 216/75,060 alleles

Filtering AF 0.256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0137% 221/1,613,954 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.288%	347
Remaining individualsnot grpmax-eligible	0.008%	12,498

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: CHMP6
Protein: p.Ala190Asp
Coding: c.569C>A
MANE Select: NM_024591
dbSNP: rs149377306
Type: single nucleotide variant
Location: chr17:80999116 (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.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
CHMP6 p.Arg49Gln 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-ala190asp (accessed [today's date]).

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