Is CHST3 p.Pro285Ser (c.853C>T) pathogenic?

CHST3 p.Pro285Ser (c.853C>T) is classified Uncertain significance in CHST3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1958); Ultra-rare (popmax 0.0158%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHST3 p.Pro285Ser (c.853C>T)?

CHST3 p.Pro285Ser (c.853C>T) is associated with Inborn genetic diseases, spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Pro285Ser (c.853C>T) in the general population?

CHST3 p.Pro285Ser (c.853C>T) is ultra-rare (popmax 0.0158%, amr) (gnomAD).

What do computational predictors say about CHST3 p.Pro285Ser (c.853C>T)?

AlphaMissense predicts likely benign (score 0.1958) — an in-silico prediction, not a clinical call.

CHST3 p.Pro285Ser

c.853C>T · rs868146865 · VCV967303

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1958	likely benign
REVEL	0.507	indeterminate
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0158% Admixed American · 9/56,898 alleles

Filtering AF 0.00822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00616%

Overall 0.000693% 11/1,587,796 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0158%	6,322
Remaining individualsnot grpmax-eligible	0.00326%	30,689

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.Pro285Ser
Coding: c.853C>T
MANE Select: NM_004273
dbSNP: rs868146865
Type: single nucleotide variant
Location: chr10:72007884 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spondyloepiphyseal dysplasia with congenital joint dislocations

Similar variants

CHST3 p.Pro285= 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-pro285ser (accessed [today's date]).

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