Is CHAT c.286+79C>T pathogenic?

CHAT c.286+79C>T is classified Likely benign in CHAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-05-07). Rare (popmax 0.293%, nfe).

How common is CHAT c.286+79C>T in the general population?

CHAT c.286+79C>T is rare (popmax 0.293%, nfe) (gnomAD).

CHAT c.286+79C>T

rs533560996 · VCV1217544

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.293%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +79	deep intronic (+79 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -2.2
Overall
CADD	7.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.293% European (non-Finnish) · 2,750/939,078 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.283% 3,681/1,301,726 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.26%	80
European (non-Finnish)grpmax	0.293%	341
Middle Eastern	0.279%	358
Remaining individualsnot grpmax-eligible	0.275%	363
Ashkenazi Jewishnot grpmax-eligible	0.206%	485
South Asian	0.143%	697
Admixed American	0.0645%	1,549
African / African-American	0.0394%	2,538

Finnish 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
Coding: c.286+79C>T
MANE Select: NM_020549
dbSNP: rs533560996
Type: single nucleotide variant
Location: chr10:49614554 (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 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
CHAT p.Arg151Ter Pathogenic/Likely pathogenic ★★ same type
CHAT p.Arg207Gly Likely pathogenic ★★ same type
CHAT p.Arg207His 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-c-286-plus-79c-t (accessed [today's date]).

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