Is DSE p.Asp26Glu (c.78C>A) pathogenic?

DSE p.Asp26Glu (c.78C>A) is classified Uncertain significance in DSE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0724); Ultra-rare (popmax 0.0561%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Asp26Glu (c.78C>A)?

DSE p.Asp26Glu (c.78C>A) is associated with Inborn genetic diseases, Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Asp26Glu (c.78C>A) in the general population?

DSE p.Asp26Glu (c.78C>A) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

What do computational predictors say about DSE p.Asp26Glu (c.78C>A)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

DSE p.Asp26Glu

c.78C>A · rs146524076 · VCV2074841

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -4.50	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 -1.1	phastCons 0.001
Regional constraint	o/e 1.05	unconstrained · MANE · 117 bp · p 0.73 · regional, not allelic
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% African / African-American · 42/74,920 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00335% 54/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,784
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Admixed American	0.005%	20,002
European (non-Finnish)	0.000254%	393,346

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.Asp26Glu
Coding: c.78C>A
MANE Select: NM_013352
dbSNP: rs146524076
Type: single nucleotide variant
Location: chr6:116399328 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, musculocontractural type 2

Similar variants

DSE p.Asp26= Likely benign ★★ 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-asp26glu (accessed [today's date]).

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