Is DSE p.Leu778= (c.2334G>T) pathogenic?

DSE p.Leu778= (c.2334G>T) is classified Benign/Likely benign in DSE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-02). Low-frequency (popmax 1.03%, sas); Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Leu778= (c.2334G>T)?

DSE p.Leu778= (c.2334G>T) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Leu778= (c.2334G>T) in the general population?

DSE p.Leu778= (c.2334G>T) is low-frequency (popmax 1.03%, sas) (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

DSE p.Leu778=

c.2334G>T · rs534248134 · VCV681762

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, sas)

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 0.61	GERP 0.3, phastCons 0.91
Overall
CADD	5.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% South Asian · 941/91,076 alleles

Filtering AF 0.978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.956%

Overall 0.063% 1,017/1,614,124 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.03%	97
Remaining individualsnot grpmax-eligible	0.0912%	1,097
Middle Eastern	0.0495%	2,021
Admixed American	0.0117%	8,575
East Asian	0.00668%	14,961
European (non-Finnish)	0.000508%	196,667

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.Leu778=
Coding: c.2334G>T
MANE Select: NM_013352
dbSNP: rs534248134
Type: single nucleotide variant
Location: chr6:116436802 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB

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.Leu778Val Uncertain significance ★ ⚠ 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
DSE p.Ala688Val 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-leu778 (accessed [today's date]).

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