Is CHAT p.Arg383Cys (c.1147C>T) pathogenic?

CHAT p.Arg383Cys (c.1147C>T) is classified Uncertain significance in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely pathogenic (0.5889); Very rare (popmax 0.000593%, nfe).

How common is CHAT p.Arg383Cys (c.1147C>T) in the general population?

CHAT p.Arg383Cys (c.1147C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CHAT p.Arg383Cys (c.1147C>T)?

AlphaMissense predicts likely pathogenic (score 0.5889) — an in-silico prediction, not a clinical call.

CHAT p.Arg383Cys

c.1147C>T · rs771822812 · VCV1694028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5889	likely pathogenic
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.93, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 32 kb · p 0.16 · regional, not allelic
Overall
CADD	33.0	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 0.000593% European (non-Finnish) · 7/1,180,044 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,112 alleles · very rare

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.Arg383Cys
Coding: c.1147C>T
MANE Select: NM_020549
dbSNP: rs771822812
Type: single nucleotide variant
Location: chr10:49646540 (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

Similar variants

CHAT p.Arg383His Uncertain significance ★★ ⚠ same residue
CHAT p.Arg383Pro Uncertain significance ★★ ⚠ same residue
CHAT p.Arg383= Likely benign ★ same residue
CHAT c.1282-2A>T Likely pathogenic ★★ same type
CHAT c.1840-9A>G Pathogenic/Likely pathogenic ★★ same type
CHAT c.698+1G>T Likely pathogenic ★★ same type
CHAT c.698+2T>C Likely pathogenic ★★ same type
CHAT p.Ala557Thr Pathogenic/Likely pathogenic ★★ same type

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-arg383cys (accessed [today's date]).

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