Is CHAT c.1111+136C>A pathogenic?

CHAT c.1111+136C>A is classified Benign in CHAT (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-16). Common (popmax 97.7%, nfe) — too common for a highly-penetrant pathogenic allele.

CHAT c.1111+136C>A

Q: How common is CHAT c.1111+136C>A in the general population?

CHAT c.1111+136C>A is common (popmax 97.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs3810951 · VCV678934

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 97.7%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +136	deep intronic (+136 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -3.7
Overall
CADD	0.921	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 97.7% European (non-Finnish) · 661,415/676,866 alleles

Filtering AF 97.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.4%

Overall 92.6% 937,759/1,013,204 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	99.3%	1
European (non-Finnish)grpmax	97.7%	1
Finnishnot grpmax-eligible	96.6%	1
Ashkenazi Jewishnot grpmax-eligible	94.3%	1
Middle Eastern	93.8%	1
South Asian	92.9%	1
Remaining individualsnot grpmax-eligible	91.5%	1
Admixed American	76.3%	1
East Asian	74.2%	1
African / African-American	57.5%	2

Amish 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.1111+136C>A
MANE Select: NM_020549
dbSNP: rs3810951
Type: single nucleotide variant
Location: chr10:49627921 (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-1111-plus-136c-a (accessed [today's date]).

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