Is CHST14 p.Arg324Pro (c.971G>C) pathogenic?

CHST14 p.Arg324Pro (c.971G>C) is classified Uncertain significance in CHST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). AlphaMissense: likely pathogenic (0.7468); Very rare (popmax 8.47e-05%, nfe); Associated with Ehlers-Danlos syndrome, musculocontractural type.

What condition is associated with CHST14 p.Arg324Pro (c.971G>C)?

CHST14 p.Arg324Pro (c.971G>C) is associated with Ehlers-Danlos syndrome, musculocontractural type (ClinVar).

How common is CHST14 p.Arg324Pro (c.971G>C) in the general population?

CHST14 p.Arg324Pro (c.971G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

What do computational predictors say about CHST14 p.Arg324Pro (c.971G>C)?

AlphaMissense predicts likely pathogenic (score 0.7468) — an in-silico prediction, not a clinical call.

CHST14 p.Arg324Pro

c.971G>C · VCV3717196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Ehlers-Danlos syndrome, musculocontractural type

Computational evidence

Protein change
AlphaMissense	0.7468	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.48, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,127 bp · p 0.038 · regional, not allelic
Overall
CADD	29.9	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 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.2e-05% 1/1,613,898 alleles · very rare exomes 0/1,461,738 · genomes 1/152,160 · joint denominator

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.Arg324Pro
Coding: c.971G>C
MANE Select: NM_130468
Type: single nucleotide variant
Location: chr15:40472184 (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.Arg324Cys Uncertain significance ★ ⚠ same residue
CHST14 p.Arg324His 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-arg324pro (accessed [today's date]).

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