Is DSE p.Ser268Leu (c.803C>T) pathogenic?

DSE p.Ser268Leu (c.803C>T) is classified Pathogenic in DSE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-09-15). AlphaMissense: likely pathogenic (0.9477); Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Ser268Leu (c.803C>T)?

DSE p.Ser268Leu (c.803C>T) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Ser268Leu (c.803C>T) in the general population?

DSE p.Ser268Leu (c.803C>T) is absent from gnomAD v4.1 (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 DSE p.Ser268Leu (c.803C>T)?

AlphaMissense predicts likely pathogenic (score 0.9477) — an in-silico prediction, not a clinical call.

DSE p.Ser268Leu

c.803C>T · rs398122361 · VCV88848

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Ehlers-Danlos syndrome, musculocontractural type 2

Computational evidence

Protein change
AlphaMissense	0.9477	likely pathogenic ✓ concordant with ClinVar
REVEL	0.447	indeterminate
SaProt	LLR -10.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 36 kb · p 6.1e-20 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSE
Protein: p.Ser268Leu
Coding: c.803C>T
MANE Select: NM_013352
dbSNP: rs398122361
Type: single nucleotide variant
Location: chr6:116431086 (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 268: a UniProt-annotated variant site (in edsmc2; shows a loss of epimerase activity towards partially desulfated dermatan sulfate; patient-derived fibroblasts show also a significant reduction in activity); 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 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-ser268leu (accessed [today's date]).

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