Is CHAT p.Phe159Ter (c.476_477delinsAG) pathogenic?

CHAT p.Phe159Ter (c.476477delinsAG) is classified Pathogenic in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). Absent from gnomAD; Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Phe159Ter (c.476_477delinsAG)?

CHAT p.Phe159Ter (c.476_477delinsAG) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Phe159Ter (c.476_477delinsAG) in the general population?

CHAT p.Phe159Ter (c.476_477delinsAG) is absent from gnomAD (gnomAD).

CHAT p.Phe159Ter

c.476_477delinsAG · rs1838635262 · VCV858247

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 0.96, 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.Phe159Ter
Coding: c.476_477delinsAG
MANE Select: NM_020549
dbSNP: rs1838635262
Type: Indel
Location: chr10:49619813 (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 159: 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

Similar variants

CHAT p.Glu490fs Likely pathogenic ★★ same condition
CHAT p.Arg548Ter 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-phe159ter (accessed [today's date]).

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