Is DSE p.Asn37Ile (c.110A>T) pathogenic?

DSE p.Asn37Ile (c.110A>T) is classified Likely benign in DSE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.386); Rare (popmax 0.167%, eas); Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Asn37Ile (c.110A>T)?

DSE p.Asn37Ile (c.110A>T) is associated with Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Asn37Ile (c.110A>T) in the general population?

DSE p.Asn37Ile (c.110A>T) is rare (popmax 0.167%, eas) (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.Asn37Ile (c.110A>T)?

AlphaMissense predicts ambiguous (score 0.386) — an in-silico prediction, not a clinical call.

DSE p.Asn37Ile

c.110A>T · rs371802983 · VCV1586828

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.386 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Ehlers-Danlos syndrome, musculocontractural type 2

Computational evidence

Protein change
AlphaMissense	0.386	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.43	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 117 bp · p 0.73 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.167% East Asian · 75/44,872 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.0057% 92/1,614,064 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.167%	598
Remaining individualsnot grpmax-eligible	0.0224%	4,465
South Asian	0.0022%	45,537
European (non-Finnish)	8.47e-05%	1,180,026

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.Asn37Ile
Coding: c.110A>T
MANE Select: NM_013352
dbSNP: rs371802983
Type: single nucleotide variant
Location: chr6:116399360 (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 37: 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.Asn37Ser 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-asn37ile (accessed [today's date]).

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