Is DSE p.Asn642= (c.1926T>C) pathogenic?

DSE p.Asn642= (c.1926T>C) is classified Benign in DSE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 99%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Asn642= (c.1926T>C)?

DSE p.Asn642= (c.1926T>C) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How is Musculocontractural Ehlers-Danlos syndrome inherited?

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

DSE p.Asn642=

Q: How common is DSE p.Asn642= (c.1926T>C) in the general population?

DSE p.Asn642= (c.1926T>C) is common (popmax 99%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1926T>C · rs560644 · VCV1166942

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 99%, eas) — too common for a highly-penetrant pathogenic allele

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 -4.1	GERP -3.9
Overall
CADD	1.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99% East Asian · 44,410/44,880 alleles

Filtering AF 98.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 98%

Overall 93.8% 1,513,580/1,614,096 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99%	1
African / African-American	98.9%	1
Middle Eastern	97.8%	1
South Asian	97.8%	1
Ashkenazi Jewishnot grpmax-eligible	96.9%	1
Admixed American	96.4%	1
Finnishnot grpmax-eligible	95.6%	1
Remaining individualsnot grpmax-eligible	94.6%	1
Amishnot grpmax-eligible	94.4%	1
European (non-Finnish)	92.6%	1

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.Asn642=
Coding: c.1926T>C
MANE Select: NM_013352
dbSNP: rs560644
Type: single nucleotide variant
Location: chr6:116436394 (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 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-asn642 (accessed [today's date]).

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