Is CHST14 p.Arg96= (c.288G>A) pathogenic?

CHST14 p.Arg96= (c.288G>A) is classified Benign/Likely benign in CHST14 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-24). Rare (popmax 0.661%, afr); Associated with Ehlers-Danlos syndrome, musculocontractural type.

What condition is associated with CHST14 p.Arg96= (c.288G>A)?

CHST14 p.Arg96= (c.288G>A) is associated with Ehlers-Danlos syndrome, musculocontractural type (ClinVar).

How common is CHST14 p.Arg96= (c.288G>A) in the general population?

CHST14 p.Arg96= (c.288G>A) is rare (popmax 0.661%, afr) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

CHST14 p.Arg96=

c.288G>A · rs371684007 · VCV210731

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.661%, afr)

Conditions

Ehlers-Danlos syndrome, musculocontractural type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.35	GERP -3
Overall
CADD	1.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.661% African / African-American · 495/74,878 alleles

Filtering AF 0.613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.594%

Overall 0.0359% 574/1,600,650 alleles · rare exomes 302/1,448,362 · genomes 272/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.661%	151
Remaining individualsnot grpmax-eligible	0.0613%	1,632
Admixed American	0.057%	1,755
South Asian	0.00331%	30,237
European (non-Finnish)	0.00034%	294,122

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.Arg96=
Coding: c.288G>A
MANE Select: NM_130468
dbSNP: rs371684007
Type: single nucleotide variant
Location: chr15:40471501 (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.Arg96Ser Likely benign ★ 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
CHST14 p.Ala15Pro 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-arg96 (accessed [today's date]).

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