Is CHST3 p.His134Tyr (c.400C>T) pathogenic?

CHST3 p.His134Tyr (c.400C>T) is classified Likely pathogenic in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). AlphaMissense: likely pathogenic (0.6336); Absent from gnomAD v4.1; Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.His134Tyr (c.400C>T)?

CHST3 p.His134Tyr (c.400C>T) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.His134Tyr (c.400C>T) in the general population?

CHST3 p.His134Tyr (c.400C>T) is absent from gnomAD v4.1 (gnomAD).

How is CHST3-related skeletal dysplasia inherited?

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

What do computational predictors say about CHST3 p.His134Tyr (c.400C>T)?

AlphaMissense predicts likely pathogenic (score 0.6336) — an in-silico prediction, not a clinical call.

CHST3 p.His134Tyr

c.400C>T · VCV4077378

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6336 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondyloepiphyseal dysplasia with congenital joint dislocations

Computational evidence

Protein change
AlphaMissense	0.6336	likely pathogenic ✓ concordant with ClinVar
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHST3
Protein: p.His134Tyr
Coding: c.400C>T
MANE Select: NM_004273
Type: single nucleotide variant
Location: chr10:72007431 (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-his134tyr (accessed [today's date]).

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