Is CHAT p.Arg29Ter (c.85A>T) pathogenic?

CHAT p.Arg29Ter (c.85A>T) is classified Pathogenic in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-31). Very rare (popmax 0.000872%, nfe).

How common is CHAT p.Arg29Ter (c.85A>T) in the general population?

CHAT p.Arg29Ter (c.85A>T) is very rare (popmax 0.000872%, nfe) (gnomAD).

CHAT p.Arg29Ter

c.85A>T · rs772025588 · VCV286608

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000872%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 15
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	26.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000872% European (non-Finnish) · 10/1,146,496 alleles

Filtering AF 0.000441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000322%

Overall 0.00071% 11/1,548,256 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00167%	59,912
European (non-Finnish)grpmax	0.000872%	114,650

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg29Ter
Coding: c.85A>T
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

Similar variants

CHAT p.Arg29Lys Uncertain significance ★ ⚠ same residue
SLC18A3 p.Arg29Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CHAT p.Arg29= 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-arg29ter (accessed [today's date]).

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