Is DSE p.Arg70His (c.209G>A) pathogenic?

DSE p.Arg70His (c.209G>A) is classified Benign/Likely benign in DSE (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-30). AlphaMissense: likely benign (0.1306); Low-frequency (popmax 3.86%, sas); Associated with Ehlers-Danlos syndrome, musculocontractural type 2.

What condition is associated with DSE p.Arg70His (c.209G>A)?

DSE p.Arg70His (c.209G>A) is associated with Ehlers-Danlos syndrome, musculocontractural type 2, Ehlers-Danlos syndrome (ClinVar).

How common is DSE p.Arg70His (c.209G>A) in the general population?

DSE p.Arg70His (c.209G>A) is low-frequency (popmax 3.86%, sas) (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.Arg70His (c.209G>A)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

DSE p.Arg70His

c.209G>A · rs147683614 · VCV517062

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.86%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome, musculocontractural type 2

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -6.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 36 kb · p 6.1e-20 · regional, not allelic
Overall
CADD	20.7	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 3.86% South Asian · 3,514/91,084 alleles

Filtering AF 3.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.71%

Overall 0.419% 6,761/1,614,186 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.86%	26
East Asian	2.72%	37
Admixed American	2.46%	41
Remaining individualsnot grpmax-eligible	0.45%	222
Middle Eastern	0.165%	606
African / African-American	0.056%	1,787
European (non-Finnish)	0.0179%	5,593
Finnishnot grpmax-eligible	0.00781%	12,804

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.Arg70His
Coding: c.209G>A
MANE Select: NM_013352
dbSNP: rs147683614
Type: single nucleotide variant
Location: chr6:116399459 (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 70: 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

Also linked: Ehlers-Danlos syndrome

For Musculocontractural Ehlers-Danlos syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DSE p.Arg70Cys Uncertain significance ★★ ⚠ same residue
TSPYL1 p.Val70Ile 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

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-arg70his (accessed [today's date]).

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