Is DSE p.Tyr867= (c.2601C>T) pathogenic?

DSE p.Tyr867= (c.2601C>T) is classified Conflicting classifications of pathogenicity in DSE (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-24). Ultra-rare (popmax 0.0168%, nfe); Associated with Ehlers-Danlos syndrome.

What condition is associated with DSE p.Tyr867= (c.2601C>T)?

DSE p.Tyr867= (c.2601C>T) is associated with Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Tyr867= (c.2601C>T) in the general population?

DSE p.Tyr867= (c.2601C>T) is ultra-rare (popmax 0.0168%, nfe) (gnomAD).

DSE p.Tyr867=

c.2601C>T · rs535021192 · VCV508454

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, nfe)

Conditions

Ehlers-Danlos syndrome

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 -4.2	GERP -3.3
Overall
CADD	3.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% European (non-Finnish) · 198/1,180,026 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0141%

Overall 0.0133% 215/1,613,814 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0168%	5,960
Middle Eastern	0.0164%	6,084
African / African-American	0.0107%	9,346
Remaining individualsnot grpmax-eligible	0.008%	12,496
South Asian	0.00329%	30,362

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.Tyr867=
Coding: c.2601C>T
MANE Select: NM_013352
dbSNP: rs535021192
Type: single nucleotide variant
Location: chr6:116437069 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, musculocontractural type 2

Similar variants

DSE p.Tyr867His 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-tyr867 (accessed [today's date]).

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