Is CHAT p.Ser39= (c.117G>C) pathogenic?

CHAT p.Ser39= (c.117G>C) is classified Likely benign in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Rare (popmax 0.308%, eas); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Ser39= (c.117G>C)?

CHAT p.Ser39= (c.117G>C) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Ser39= (c.117G>C) in the general population?

CHAT p.Ser39= (c.117G>C) is rare (popmax 0.308%, eas) (gnomAD).

CHAT p.Ser39=

c.117G>C · rs768179285 · VCV1132438

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.308%, 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 -0.026	GERP -2
Overall
CADD	6.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.308% East Asian · 126/40,894 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.248%

Overall 0.0084% 130/1,547,820 alleles · rare exomes 128/1,395,658 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.308%	325
Remaining individualsnot grpmax-eligible	0.00334%	29,929
Admixed American	0.00196%	50,968
European (non-Finnish)	8.72e-05%	1,146,289

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.Ser39=
Coding: c.117G>C
MANE Select: NM_020549
dbSNP: rs768179285
Type: single nucleotide variant
Location: chr10:49614306 (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 39: 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 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
CHAT p.Arg207His 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-ser39 (accessed [today's date]).

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