Is CHIT1 p.Arg269= (c.807C>T) pathogenic?

CHIT1 p.Arg269= (c.807C>T) is classified Conflicting classifications of pathogenicity in CHIT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-11-16). Rare (popmax 0.252%, sas); Associated with Chitotriosidase deficiency.

What condition is associated with CHIT1 p.Arg269= (c.807C>T)?

CHIT1 p.Arg269= (c.807C>T) is associated with Chitotriosidase deficiency (ClinVar).

How common is CHIT1 p.Arg269= (c.807C>T) in the general population?

CHIT1 p.Arg269= (c.807C>T) is rare (popmax 0.252%, sas) (gnomAD).

CHIT1 p.Arg269=

c.807C>T · rs560698644 · VCV294922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.252%, sas)

Conditions

Chitotriosidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.9
Overall
CADD	0.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.252% South Asian · 229/91,046 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.214%

Overall 0.0148% 238/1,613,534 alleles · rare exomes 226/1,461,218 · genomes 12/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.252%	398
Middle Eastern	0.0178%	5,616
Remaining individualsnot grpmax-eligible	0.00801%	12,489
East Asian	0.00446%	22,440
European (non-Finnish)	8.47e-05%	1,179,965

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: CHIT1
Protein: p.Arg269=
Coding: c.807C>T
MANE Select: NM_003465
dbSNP: rs560698644
Type: single nucleotide variant
Location: chr1:203219772 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 23 PDB
Residue 269: the gh18 domain; a β-strand

Full CHIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Chitotriosidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHIT1 p.Arg269Cys Benign ★ ⚠ same residue
CHIT1 p.Arg269His Uncertain significance ★ ⚠ same residue
CHIT1 c.-13G>A Uncertain significance ★★ same condition
CHIT1 c.*119C>T Uncertain significance ★★ same condition
CHIT1 p.Arg128His Uncertain significance ★★ ⚠ same condition
CHIT1 p.Arg432Trp Uncertain significance ★★ ⚠ same condition
CHIT1 p.Pro451Arg Uncertain significance ★★ ⚠ same condition
CHIT1 c.25+8G>T Likely benign ★★ 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/chit1-p-arg269 (accessed [today's date]).

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