Is CHIT1 p.Ala239= (c.717C>T) pathogenic?

CHIT1 p.Ala239= (c.717C>T) is classified Likely benign in CHIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). Ultra-rare (popmax 0.0147%, afr); Associated with Chitotriosidase deficiency.

What condition is associated with CHIT1 p.Ala239= (c.717C>T)?

CHIT1 p.Ala239= (c.717C>T) is associated with Chitotriosidase deficiency (ClinVar).

How common is CHIT1 p.Ala239= (c.717C>T) in the general population?

CHIT1 p.Ala239= (c.717C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

CHIT1 p.Ala239=

c.717C>T · rs775684280 · VCV2201761

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

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 -4.9	GERP -3.4
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,940 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000682% 11/1,614,010 alleles · ultra-rare exomes 5/1,461,792 · genomes 6/152,218 · joint denominator

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.Ala239=
Coding: c.717C>T
MANE Select: NM_003465
dbSNP: rs775684280
Type: single nucleotide variant
Location: chr1:203222214 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.72 · 23 PDB
Residue 239: the gh18 domain; an α-helix

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-ala239 (accessed [today's date]).

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