Is CHAT p.Arg28fs (c.84_91del) pathogenic?

CHAT p.Arg28fs (c.8491del) is classified Likely pathogenic in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Arg28fs (c.84_91del)?

CHAT p.Arg28fs (c.84_91del) is associated with congenital myasthenic syndrome 6 (ClinVar).

CHAT p.Arg28fs

c.84_91del · VCV3595466

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -2.3, phastCons 0.98
Region caveats
Repeat context	tandem	G-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CHAT
Protein: p.Arg28fs
Coding: c.84_91del
MANE Select: NM_020549
Type: Deletion
Location: chr10:49614269 (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 28: the 'disordered' region

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 p.Arg28Ser Uncertain significance ★★ ⚠ same residue
CHAT p.Arg28Gly Uncertain significance ★ ⚠ same residue
CHAT p.Arg28= Likely benign ★ same residue
CHAT p.Asp328fs Pathogenic/Likely pathogenic ★★ same condition
CHAT p.Cys453_Glu455delinsTer Pathogenic/Likely pathogenic ★★ same condition
CHAT p.Gln223fs Pathogenic ★★ same condition
CHAT p.Gly617fs Pathogenic/Likely pathogenic ★★ same condition
CHAT p.Pro138fs 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-arg28fs (accessed [today's date]).

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