Is CHST3 p.Pro164Leu (c.491C>T) pathogenic?

CHST3 p.Pro164Leu (c.491C>T) is classified Pathogenic in CHST3 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9822); Very rare (popmax 0.00439%, sas); Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.Pro164Leu (c.491C>T)?

CHST3 p.Pro164Leu (c.491C>T) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Pro164Leu (c.491C>T) in the general population?

CHST3 p.Pro164Leu (c.491C>T) is very rare (popmax 0.00439%, sas) (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.Pro164Leu (c.491C>T)?

AlphaMissense predicts likely pathogenic (score 0.9822) — an in-silico prediction, not a clinical call.

CHST3 p.Pro164Leu

c.491C>T · rs771866012 · VCV478823

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondyloepiphyseal dysplasia with congenital joint dislocations

Computational evidence

Protein change
AlphaMissense	0.9822	likely pathogenic ✓ concordant with ClinVar · top 9% in CHST3
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -14.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	32.0	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

Grpmax group 0.00439% South Asian · 4/91,028 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000276% 4/1,451,634 alleles · very rare

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.Pro164Leu
Coding: c.491C>T
MANE Select: NM_004273
dbSNP: rs771866012
Type: single nucleotide variant
Location: chr10:72007522 (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.Pro164= Likely benign ★ same residue
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

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-pro164leu (accessed [today's date]).

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