Is DSE p.Thr72= (c.216G>A) pathogenic?

DSE p.Thr72= (c.216G>A) is classified Benign/Likely benign in DSE (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-23). Rare (popmax 0.478%, afr); Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Thr72= (c.216G>A)?

DSE p.Thr72= (c.216G>A) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Thr72= (c.216G>A) in the general population?

DSE p.Thr72= (c.216G>A) is rare (popmax 0.478%, afr) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

DSE p.Thr72=

c.216G>A · rs61747210 · VCV668223

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.478%, afr)

Conditions

Ehlers-Danlos syndrome, musculocontractural type 2

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 -20
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.478% African / African-American · 359/75,058 alleles

Filtering AF 0.437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.422%

Overall 0.0266% 429/1,614,208 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.478%	209
Admixed American	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.04%	2,500
East Asian	0.00668%	14,959
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,019

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: DSE
Protein: p.Thr72=
Coding: c.216G>A
MANE Select: NM_013352
dbSNP: rs61747210
Type: single nucleotide variant
Location: chr6:116399466 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB
Residue 72: an α-helix

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

Disease context

Ehlers-Danlos syndrome, musculocontractural type 2 — 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

DSE p.Thr72Met Uncertain significance ★★ ⚠ same residue
TSPYL1 p.Gln72Ter Likely pathogenic ★ same residue
DSE c.416+1G>A Likely pathogenic ★★ same condition
DSE p.Ala122Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala135Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala408Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala54Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala584Val 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/dse-p-thr72 (accessed [today's date]).

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