Is DSE p.Leu237= (c.711G>C) pathogenic?

DSE p.Leu237= (c.711G>C) is classified Benign/Likely benign in DSE (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.949%, nfe); Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Leu237= (c.711G>C)?

DSE p.Leu237= (c.711G>C) is associated with Ehlers-Danlos syndrome, musculocontractural type 2, Ehlers-Danlos syndrome (ClinVar).

How common is DSE p.Leu237= (c.711G>C) in the general population?

DSE p.Leu237= (c.711G>C) is rare (popmax 0.949%, nfe) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

DSE p.Leu237=

c.711G>C · rs140034597 · VCV384822

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.949%, nfe)

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 4.4	GERP 0.47, phastCons 1
Overall
CADD	8.935	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.949% European (non-Finnish) · 11,200/1,180,040 alleles

Filtering AF 0.934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.928%

Overall 0.764% 12,333/1,613,968 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.949%	105
Finnishnot grpmax-eligible	0.655%	153
Remaining individualsnot grpmax-eligible	0.563%	178
Ashkenazi Jewishnot grpmax-eligible	0.372%	269
Amishnot grpmax-eligible	0.219%	456
Admixed American	0.143%	698
African / African-American	0.131%	765
South Asian	0.0681%	1,468
Middle Eastern	0.0669%	1,495

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.Leu237=
Coding: c.711G>C
MANE Select: NM_013352
dbSNP: rs140034597
Type: single nucleotide variant
Location: chr6:116430994 (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 237: 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

Also linked: Ehlers-Danlos syndrome

For Musculocontractural Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
DSE p.Ala688Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala710Val 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-leu237 (accessed [today's date]).

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