Is CHAT p.Arg652Gln (c.1955G>A) pathogenic?

CHAT p.Arg652Gln (c.1955G>A) is classified Likely benign in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0773); Rare (popmax 0.31%, eas); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Arg652Gln (c.1955G>A)?

CHAT p.Arg652Gln (c.1955G>A) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Arg652Gln (c.1955G>A) in the general population?

CHAT p.Arg652Gln (c.1955G>A) is rare (popmax 0.31%, eas) (gnomAD).

What do computational predictors say about CHAT p.Arg652Gln (c.1955G>A)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

CHAT p.Arg652Gln

c.1955G>A · rs116628504 · VCV703582

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.31%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -3.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -4.4
Regional constraint	o/e 0.89	unconstrained · MANE · 16 kb · p 0.024 · regional, not allelic
Overall
CADD	14.94	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

Grpmax group 0.31% East Asian · 139/44,890 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.0212% 343/1,614,220 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.31%	323
Remaining individualsnot grpmax-eligible	0.0288%	3,473
European (non-Finnish)	0.0147%	6,821
African / African-American	0.0133%	7,505
Admixed American	0.00333%	30,008
South Asian	0.0011%	91,086

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.Arg652Gln
Coding: c.1955G>A
MANE Select: NM_020549
dbSNP: rs116628504
Type: single nucleotide variant
Location: chr10:49662760 (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.Arg652= 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-arg652gln (accessed [today's date]).

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