Is CHAT p.Ser279del (c.833CCT[1]) pathogenic?

CHAT p.Ser279del (c.833CCT[1]) is classified Conflicting classifications of pathogenicity in CHAT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-04). Rare (popmax 0.476%, afr); Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Ser279del (c.833CCT[1])?

CHAT p.Ser279del (c.833CCT[1]) is associated with congenital myasthenic syndrome 6 (ClinVar).

How common is CHAT p.Ser279del (c.833CCT[1]) in the general population?

CHAT p.Ser279del (c.833CCT[1]) is rare (popmax 0.476%, afr) (gnomAD).

CHAT p.Ser279del

c.833CCT[1] · rs560648873 · VCV497297

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.476%, afr)

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Overall
CADD	15.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.476% African / African-American · 357/75,048 alleles

Filtering AF 0.435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.0304% 490/1,613,708 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.476%	210
Admixed American	0.103%	968
Middle Eastern	0.0838%	1,193
Remaining individualsnot grpmax-eligible	0.0592%	1,689
European (non-Finnish)	0.00246%	40,687

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.Ser279del
Coding: c.833CCT[1]
MANE Select: NM_020549
dbSNP: rs560648873
Type: Microsatellite
Location: chr10:49625551 (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 279: 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.Ser279= Likely benign ★ same residue
CHAT c.1382+2_1382+3del Likely pathogenic ★ same condition
CHAT p.Asn569del Uncertain significance ★ same condition
CHAT p.Ser705del Conflicting classifications of pathogenicity ★ same condition
CHAT c.1282-14_1282-13del Likely benign ★ same condition
CHAT c.1777-17_1777-16del Likely benign ★ same condition
CHAT c.286+11GGGCT[4] Likely benign ★ same condition
CHAT c.286+9_286+11del Likely benign ★ 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-ser279del (accessed [today's date]).

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