Is CHAT p.Asn569del (c.1703ACA[1]) pathogenic?

CHAT p.Asn569del (c.1703ACA[1]) is classified Uncertain significance in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). Very rare (popmax 0.00134%, afr); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Asn569del (c.1703ACA[1])?

CHAT p.Asn569del (c.1703ACA[1]) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Asn569del (c.1703ACA[1]) in the general population?

CHAT p.Asn569del (c.1703ACA[1]) is very rare (popmax 0.00134%, afr) (gnomAD).

CHAT p.Asn569del

c.1703ACA[1] · rs139324199 · VCV1997632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	18.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,902 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,902
South Asian	0.0011%	91,066
European (non-Finnish)	0.000254%	393,349

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: CHAT
Protein: p.Asn569del
Coding: c.1703ACA[1]
MANE Select: NM_020549
dbSNP: rs139324199
Type: Microsatellite
Location: chr10:49655163 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.73 · 8 PDB
Residue 569: a β-strand

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

Disease context

congenital myasthenic syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHAT c.1382+2_1382+3del Likely pathogenic ★ same condition
CHAT p.Ser279del Conflicting classifications of pathogenicity ★ same condition
CHAT p.Ser705del Conflicting classifications of pathogenicity ★ same condition
CHAT c.1282-14_1282-13del Likely benign ★ same condition
CHAT c.1777-17_1777-16del Likely benign ★ same condition
CHAT c.286+11GGGCT[4] Likely benign ★ same condition
CHAT c.286+9_286+11del Likely benign ★ same condition
CHAT c.1282-2A>T Likely pathogenic ★★ same condition

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/chat-p-asn569del (accessed [today's date]).

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