Is CHAT p.Ala120Thr (c.358G>A) pathogenic?

CHAT p.Ala120Thr (c.358G>A) is classified Benign/Likely benign in CHAT (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.07); Common (popmax 27.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with congenital myasthenic syndrome 6.

What condition is associated with CHAT p.Ala120Thr (c.358G>A)?

CHAT p.Ala120Thr (c.358G>A) is associated with congenital myasthenic syndrome 6 (ClinVar).

What do computational predictors say about CHAT p.Ala120Thr (c.358G>A)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

CHAT p.Ala120Thr

Q: How common is CHAT p.Ala120Thr (c.358G>A) in the general population?

CHAT p.Ala120Thr (c.358G>A) is common (popmax 27.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.358G>A · rs3810950 · VCV128724

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 27.6%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 6

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.87	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 1.1	GERP -3.8, phastCons 0.006
Regional constraint	o/e 1.06	unconstrained · MANE · 32 kb · p 0.16 · regional, not allelic
Overall
CADD	13.48	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 27.6% Middle Eastern · 1,673/6,060 alleles

Filtering AF 27.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.2%

Overall 23.7% 381,427/1,610,550 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	27.6%	4
South Asian	27.6%	4
Amishnot grpmax-eligible	26.8%	4
European (non-Finnish)	25.5%	4
Ashkenazi Jewishnot grpmax-eligible	24.4%	4
Remaining individualsnot grpmax-eligible	23.3%	4
Finnishnot grpmax-eligible	18.5%	5
East Asian	17.1%	6
Admixed American	15.8%	6
African / African-American	4.41%	23

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.Ala120Thr
Coding: c.358G>A
MANE Select: NM_020549
dbSNP: rs3810950
Type: single nucleotide variant
Location: chr10:49616573 (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 120: a UniProt-annotated variant site (in)

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-ala120thr (accessed [today's date]).

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