Is CHIT1 p.Ile96= (c.288C>T) pathogenic?

CHIT1 p.Ile96= (c.288C>T) is classified Likely benign in CHIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). Ultra-rare (popmax 0.0329%, nfe); Associated with Chitotriosidase deficiency.

What condition is associated with CHIT1 p.Ile96= (c.288C>T)?

CHIT1 p.Ile96= (c.288C>T) is associated with Chitotriosidase deficiency (ClinVar).

How common is CHIT1 p.Ile96= (c.288C>T) in the general population?

CHIT1 p.Ile96= (c.288C>T) is ultra-rare (popmax 0.0329%, nfe) (gnomAD).

CHIT1 p.Ile96=

c.288C>T · rs539275442 · VCV2058229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, nfe)

Conditions

Chitotriosidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.7	GERP -3.4
Overall
CADD	0.946	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% European (non-Finnish) · 388/1,179,936 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.0262% 423/1,613,650 alleles · ultra-rare exomes 408/1,461,760 · genomes 15/151,890 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.024%	4,165
South Asian	0.0176%	5,691
African / African-American	0.00535%	18,701

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.Ile96=
Coding: c.288C>T
MANE Select: NM_003465
dbSNP: rs539275442
Type: single nucleotide variant
Location: chr1:203225074 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 23 PDB
Residue 96: 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 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
CHIT1 c.258-6T>C Benign ★★ same condition
CHIT1 p.Ala442Gly 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-ile96 (accessed [today's date]).

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