Is CHST3 p.Ser173Phe (c.518C>T) pathogenic?

CHST3 p.Ser173Phe (c.518C>T) is classified Conflicting classifications of pathogenicity in CHST3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.1525); Ultra-rare (popmax 0.0751%, amr); Associated with spondyloepiphyseal dysplasia with congenital joint dislocations.

What condition is associated with CHST3 p.Ser173Phe (c.518C>T)?

CHST3 p.Ser173Phe (c.518C>T) is associated with spondyloepiphyseal dysplasia with congenital joint dislocations (ClinVar).

How common is CHST3 p.Ser173Phe (c.518C>T) in the general population?

CHST3 p.Ser173Phe (c.518C>T) is ultra-rare (popmax 0.0751%, amr) (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.Ser173Phe (c.518C>T)?

AlphaMissense predicts likely benign (score 0.1525) — an in-silico prediction, not a clinical call.

CHST3 p.Ser173Phe

c.518C>T · rs751961615 · VCV445944

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1525 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0751%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondyloepiphyseal dysplasia with congenital joint dislocations

Computational evidence

Protein change
AlphaMissense	0.1525	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -9.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.4, phastCons 0.97
Regional constraint	o/e 1.03	unconstrained · MANE · 2,625 bp · p 0.38 · regional, not allelic
Overall
CADD	19.46	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 0.0751% Admixed American · 45/59,944 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.0028% 45/1,606,012 alleles · ultra-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.Ser173Phe
Coding: c.518C>T
MANE Select: NM_004273
dbSNP: rs751961615
Type: single nucleotide variant
Location: chr10:72007549 (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-ser173phe (accessed [today's date]).

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