Is DSP p.Gln616= (c.1848G>A) pathogenic?

DSP p.Gln616= (c.1848G>A) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-27). Very rare (popmax 0.00223%, eas); Associated with lethal acantholytic epidermolysis bullosa.

What condition is associated with DSP p.Gln616= (c.1848G>A)?

DSP p.Gln616= (c.1848G>A) is associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Gln616= (c.1848G>A) in the general population?

DSP p.Gln616= (c.1848G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Lethal acantholytic erosive disorder inherited?

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

DSP p.Gln616=

c.1848G>A · rs1215425090 · VCV911906

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

lethal acantholytic epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Overall
CADD	10.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.2e-05% 1/1,614,184 alleles · very rare exomes 1/1,461,892 · genomes 0/152,292 · joint denominator

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: DSP
Protein: p.Gln616=
Coding: c.1848G>A
MANE Select: NM_004415
dbSNP: rs1215425090
Type: single nucleotide variant
Location: chr6:7571529 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 616: a UniProt-annotated variant site (in dcwhkta; reduces dsp protein abundance and results in accumulation of dsp membrane-associated and intracellular focal aggregates. decreases localization of dsg1, jup and gja1 to intercellular junctions. reduces the number of desmosomes in the suprabasal layers of the skin leading to wider intercellular spaces between suprabasal cells. defects in lipid processing and secretion with premature secretion of lamellar bodies which show defective structure and supramolecular organization); an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8)

Full DSP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lethal acantholytic epidermolysis bullosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 woolly hair-skin fragility syndrome

For Lethal acantholytic erosive disorder (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

DSP p.Gln616Ter Pathogenic ★ same residue
DSP p.Gln616Arg Uncertain significance ★ same residue
DSP p.Gln616Glu Uncertain significance ★ same residue
DSP p.Gln616Pro Pathogenic same residue
DSP c.1141-2A>T Likely pathogenic ★★ same condition
DSP c.1266+2T>C Likely pathogenic ★★ same condition
DSP c.1574+1G>A Likely pathogenic ★★ same condition
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ 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/dsp-p-gln616 (accessed [today's date]).

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