Is CHST14 p.Val104= (c.312G>T) pathogenic?

CHST14 p.Val104= (c.312G>T) is classified Likely benign in CHST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-29). Very rare (popmax 0.0022%, sas); Associated with Ehlers-Danlos syndrome, musculocontractural type.

What condition is associated with CHST14 p.Val104= (c.312G>T)?

CHST14 p.Val104= (c.312G>T) is associated with Ehlers-Danlos syndrome, musculocontractural type (ClinVar).

How common is CHST14 p.Val104= (c.312G>T) in the general population?

CHST14 p.Val104= (c.312G>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

CHST14 p.Val104=

c.312G>T · rs1894346180 · VCV2986177

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.52, phastCons 1
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,776 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000125% 2/1,600,846 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: CHST14
Protein: p.Val104=
Coding: c.312G>T
MANE Select: NM_130468
dbSNP: rs1894346180
Type: single nucleotide variant
Location: chr15:40471525 (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.Val104Met 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
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-val104 (accessed [today's date]).

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