Is CHST3 p.Ala407= (c.1221G>A) pathogenic?

CHST3 p.Ala407= (c.1221G>A) is classified Likely benign in CHST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). Absent from gnomAD v4.1; Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.Ala407= (c.1221G>A)?

CHST3 p.Ala407= (c.1221G>A) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Ala407= (c.1221G>A) in the general population?

CHST3 p.Ala407= (c.1221G>A) 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.

CHST3 p.Ala407=

c.1221G>A · VCV3711389

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,570)

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 0.1	GERP -3.2, phastCons 0.091
Overall
CADD	4.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,576,570). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHST3
Protein: p.Ala407=
Coding: c.1221G>A
MANE Select: NM_004273
Type: single nucleotide variant
Location: chr10:72008252 (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-ala407 (accessed [today's date]).

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