Is CHAT p.Glu737fs (c.2209del) pathogenic?

CHAT p.Glu737fs (c.2209del) is classified Uncertain significance in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). Absent from gnomAD.

How common is CHAT p.Glu737fs (c.2209del) in the general population?

CHAT p.Glu737fs (c.2209del) is absent from gnomAD (gnomAD).

CHAT p.Glu737fs

c.2209del · rs2538897332 · VCV1804817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -1.2, 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.Glu737fs
Coding: c.2209del
MANE Select: NM_020549
dbSNP: rs2538897332
Type: Deletion
Location: chr10:49665007 (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 737: the 'disordered' region

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

Similar variants

CHAT p.Glu737Asp Uncertain significance ★★ ⚠ same residue
CHAT p.Asp328fs Pathogenic/Likely pathogenic ★★ same type
CHAT p.Cys453_Glu455delinsTer Pathogenic/Likely pathogenic ★★ same type
CHAT p.Gln223fs Pathogenic ★★ same type
CHAT p.Gly617fs Pathogenic/Likely pathogenic ★★ same type
CHAT p.Pro138fs Likely pathogenic ★★ same type
CHAT p.Gly2_Leu3insTer Uncertain significance ★★ same type
CHAT c.1977+1_1977+9del Likely pathogenic ★ same type

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-glu737fs (accessed [today's date]).

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