Is DSE p.Ala161fs (c.480del) pathogenic?

DSE p.Ala161fs (c.480del) is classified Pathogenic in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Absent from gnomAD; Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Ala161fs (c.480del)?

DSE p.Ala161fs (c.480del) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Ala161fs (c.480del) in the general population?

DSE p.Ala161fs (c.480del) is absent from gnomAD (gnomAD).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

DSE p.Ala161fs

c.480del · rs2482243158 · VCV2119102

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ehlers-Danlos syndrome, musculocontractural type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSE
Protein: p.Ala161fs
Coding: c.480del
MANE Select: NM_013352
dbSNP: rs2482243158
Type: Deletion
Location: chr6:116426637 (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 161: 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.Ala161= Likely benign ★★ same residue
DSE p.Gly874del Benign/Likely benign ★★ same condition
DSE p.Gln271fs Pathogenic ★ same condition
DSE p.Arg933fs Uncertain significance ★ same condition
DSE p.Gln828fs Uncertain significance ★ same condition
DSE p.Pro497fs Uncertain significance ★ same condition
TSPYL1 p.Ala161Thr Uncertain significance ★ ⚠ same residue
DSE c.416+1G>A Likely pathogenic ★★ 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-ala161fs (accessed [today's date]).

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