Is CHAT p.Tyr273= (c.819C>T) pathogenic?

CHAT p.Tyr273= (c.819C>T) is classified Likely benign in CHAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-28). Ultra-rare (popmax 0.034%, mid); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Tyr273= (c.819C>T)?

CHAT p.Tyr273= (c.819C>T) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Tyr273= (c.819C>T) in the general population?

CHAT p.Tyr273= (c.819C>T) is ultra-rare (popmax 0.034%, mid) (gnomAD).

CHAT p.Tyr273=

c.819C>T · rs1838886496 · VCV2998605

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, mid)

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.26	GERP -3.1, phastCons 0.93
Overall
CADD	3.715	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% Middle Eastern · 2/5,874 alleles

Filtering AF 0.00599% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.000496% 8/1,613,684 alleles · ultra-rare exomes 7/1,461,440 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.034%	2,937
African / African-American	0.00534%	18,734
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	8.47e-05%	1,179,994

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHAT
Protein: p.Tyr273=
Coding: c.819C>T
MANE Select: NM_020549
dbSNP: rs1838886496
Type: single nucleotide variant
Location: chr10:49625539 (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 273: 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.Tyr273Cys Uncertain significance ★ ⚠ same residue
SLC18A3 p.Arg273= Uncertain significance ★ same residue
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
CHAT p.Ala557Thr Pathogenic/Likely pathogenic ★★ same condition
CHAT p.Arg151Ter Pathogenic/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-tyr273 (accessed [today's date]).

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