Is CHST3 p.Ile38= (c.114C>T) pathogenic?

CHST3 p.Ile38= (c.114C>T) is classified Likely benign in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). Ultra-rare (popmax 0.03%, amr); Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.Ile38= (c.114C>T)?

CHST3 p.Ile38= (c.114C>T) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Ile38= (c.114C>T) in the general population?

CHST3 p.Ile38= (c.114C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

How is CHST3-related skeletal dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CHST3 p.Ile38=

c.114C>T · rs374590185 · VCV1156567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

spondyloepiphyseal dysplasia with congenital joint dislocations

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 -0.29	GERP -1.7, phastCons 0.39
Overall
CADD	9.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,994 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00297% 48/1,613,948 alleles · ultra-rare exomes 25/1,461,880 · genomes 23/152,068 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
African / African-American	0.0174%	5,760
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.00439%	22,769
European (non-Finnish)	0.000593%	168,575

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: CHST3
Protein: p.Ile38=
Coding: c.114C>T
MANE Select: NM_004273
dbSNP: rs374590185
Type: single nucleotide variant
Location: chr10:72005956 (GRCh38)
Gene constraint: LOEUF 1.119 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.58

Full CHST3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondyloepiphyseal dysplasia with congenital joint dislocations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CHST3-related skeletal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

CHST3 p.Arg221Cys Pathogenic/Likely pathogenic ★★ same condition
CHST3 p.Glu230Ter Pathogenic/Likely pathogenic ★★ same condition
CHST3 p.Phe159Ile Pathogenic/Likely pathogenic ★★ same condition
CHST3 c.*57G>T Uncertain significance ★★ same condition
CHST3 c.*66G>T Uncertain significance ★★ same condition
CHST3 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala129Glu Uncertain significance ★★ ⚠ same condition
CHST3 p.Ala182Thr Uncertain significance ★★ ⚠ 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/chst3-p-ile38 (accessed [today's date]).

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