Is CHAT p.Leu282Phe (c.844C>T) pathogenic?

CHAT p.Leu282Phe (c.844C>T) is classified Uncertain significance in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-07). AlphaMissense: likely benign (0.2152); Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Leu282Phe (c.844C>T)?

CHAT p.Leu282Phe (c.844C>T) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Leu282Phe (c.844C>T) in the general population?

CHAT p.Leu282Phe (c.844C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHAT p.Leu282Phe (c.844C>T)?

AlphaMissense predicts likely benign (score 0.2152) — an in-silico prediction, not a clinical call.

CHAT p.Leu282Phe

c.844C>T · rs1390587206 · VCV2139437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2152 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
AlphaMissense	0.2152	likely benign
REVEL	0.734	pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 32 kb · p 0.16 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHAT
Protein: p.Leu282Phe
Coding: c.844C>T
MANE Select: NM_020549
dbSNP: rs1390587206
Type: single nucleotide variant
Location: chr10:49625564 (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 282: a β-strand

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.Leu282= Likely benign ★ 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
CHAT p.Arg207Gly 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-leu282phe (accessed [today's date]).

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