Is CHST14 p.Arg231= (c.693A>T) pathogenic?

CHST14 p.Arg231= (c.693A>T) is classified Uncertain significance in CHST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Very rare (popmax 0.00167%, amr); Associated with Ehlers-Danlos syndrome, musculocontractural type.

What condition is associated with CHST14 p.Arg231= (c.693A>T)?

CHST14 p.Arg231= (c.693A>T) is associated with Ehlers-Danlos syndrome, musculocontractural type (ClinVar).

How common is CHST14 p.Arg231= (c.693A>T) in the general population?

CHST14 p.Arg231= (c.693A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

CHST14 p.Arg231=

c.693A>T · rs1228128596 · VCV1932725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Ehlers-Danlos syndrome, musculocontractural type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.51	GERP -3.8
Overall
CADD	8.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Overall 0.000124% 2/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: CHST14
Protein: p.Arg231=
Coding: c.693A>T
MANE Select: NM_130468
dbSNP: rs1228128596
Type: single nucleotide variant
Location: chr15:40471906 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.17

Full CHST14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome, musculocontractural type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Musculocontractural Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CHST14 p.Arg231Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CHST14 p.Arg231Gly Uncertain significance ★ ⚠ same residue
CHST14 p.Arg213Pro Likely pathogenic ★★ same condition
CHST14 p.Arg320Ter Likely pathogenic ★★ same condition
CHST14 p.Gln204Ter Pathogenic/Likely pathogenic ★★ same condition
CHST14 p.Glu262Lys Pathogenic/Likely pathogenic ★★ same condition
CHST14 p.Tyr293Cys Pathogenic/Likely pathogenic ★★ same condition
CHST14 p.Ala11Val 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/chst14-p-arg231 (accessed [today's date]).

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