Is CHAT p.Glu490fs (c.1468_1470delinsC) pathogenic?

CHAT p.Glu490fs (c.14681470delinsC) is classified Likely pathogenic in CHAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-05). Absent from gnomAD; Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Glu490fs (c.1468_1470delinsC)?

CHAT p.Glu490fs (c.1468_1470delinsC) is associated with congenital myasthenic syndrome 6, congenital myasthenic syndrome (ClinVar).

How common is CHAT p.Glu490fs (c.1468_1470delinsC) in the general population?

CHAT p.Glu490fs (c.1468_1470delinsC) is absent from gnomAD (gnomAD).

CHAT p.Glu490fs

c.1468_1470delinsC · rs2538864425 · VCV1705068

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 10 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHAT
Protein: p.Glu490fs
Coding: c.1468_1470delinsC
MANE Select: NM_020549
dbSNP: rs2538864425
Type: Indel
Location: chr10:49649593 (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 490: an α-helix

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

Also linked: congenital myasthenic syndrome

Similar variants

CHAT p.Arg548Ter Pathogenic ★ same condition
CHAT p.Phe159Ter Pathogenic ★ same condition
CHAT p.Ala171Asn Uncertain significance ★ same condition
CHAT p.Arg66fs Conflicting classifications of pathogenicity ★ same condition
CHAT c.1282-2A>T Likely pathogenic ★★ same condition
CHAT c.1840-9A>G Pathogenic/Likely pathogenic ★★ same condition
CHAT c.698+1G>T Likely pathogenic ★★ same condition
CHAT c.698+2T>C 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-glu490fs (accessed [today's date]).

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