Is CHAT p.Pro138fs (c.413del) pathogenic?

CHAT p.Pro138fs (c.413del) is classified Likely pathogenic in CHAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-06). Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Pro138fs (c.413del)?

CHAT p.Pro138fs (c.413del) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Pro138fs (c.413del) in the general population?

CHAT p.Pro138fs (c.413del) is absent from gnomAD v4.1 (gnomAD).

CHAT p.Pro138fs

c.413del · rs1838630775 · VCV2680738

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,708)

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,708). 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.Pro138fs
Coding: c.413del
MANE Select: NM_020549
dbSNP: rs1838630775
Type: Deletion
Location: chr10:49619746 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.73 · 8 PDB

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.Pro138Gln Uncertain significance ★ ⚠ same residue
CHAT p.Pro138Leu Uncertain significance ★ ⚠ same residue
CHAT p.Pro138= 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.Gly2_Leu3insTer Uncertain significance ★★ 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-pro138fs (accessed [today's date]).

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