Is CHAT p.Arg29= (c.85A>C) pathogenic?

CHAT p.Arg29= (c.85A>C) is classified Likely benign in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). Rare (popmax 0.555%, eas); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Arg29= (c.85A>C)?

CHAT p.Arg29= (c.85A>C) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Arg29= (c.85A>C) in the general population?

CHAT p.Arg29= (c.85A>C) is rare (popmax 0.555%, eas) (gnomAD).

CHAT p.Arg29=

c.85A>C · rs772025588 · VCV772954

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.555%, eas)

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -2.2, phastCons 0.047
Overall
CADD	5.104	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.555% East Asian · 227/40,866 alleles

Filtering AF 0.496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.473%

Overall 0.0149% 231/1,548,364 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.555%	180
Remaining individualsnot grpmax-eligible	0.00667%	14,983

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.Arg29=
Coding: c.85A>C
MANE Select: NM_020549
dbSNP: rs772025588
Type: single nucleotide variant
Location: chr10:49614274 (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 29: the 'disordered' region

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.Arg29Lys Uncertain significance ★ ⚠ same residue
CHAT p.Arg29Ter Pathogenic ★ same residue
SLC18A3 p.Arg29Trp Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg29 (accessed [today's date]).

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