Is DSP p.Lys1907Ter (c.5719A>T) pathogenic?

DSP p.Lys1907Ter (c.5719A>T) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-01). Absent from gnomAD v4.1; Associated with lethal acantholytic epidermolysis bullosa.

What condition is associated with DSP p.Lys1907Ter (c.5719A>T)?

DSP p.Lys1907Ter (c.5719A>T) is associated with lethal acantholytic epidermolysis bullosa (ClinVar).

How common is DSP p.Lys1907Ter (c.5719A>T) in the general population?

DSP p.Lys1907Ter (c.5719A>T) is absent from gnomAD v4.1 (gnomAD).

How is Lethal acantholytic erosive disorder inherited?

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

DSP p.Lys1907Ter

c.5719A>T · VCV4015117

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

lethal acantholytic epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (24 of 24) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.4, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Lys1907Ter
Coding: c.5719A>T
MANE Select: NM_004415
Type: single nucleotide variant
Location: chr6:7582981 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1907: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); the 'central fibrous rod domain' region; the 'binds to telomeres' region; 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

For Lethal acantholytic erosive disorder (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

DSP p.Lys1907Asn Uncertain significance ★★ ⚠ same residue
DSP p.Arg1400Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1934Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Glu1081Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Lys2356Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Tyr1169Ter Likely pathogenic ★★ same condition
DSP p.Tyr2547Ter Pathogenic/Likely pathogenic ★★ same condition
DSP c.1044+3A>C 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/dsp-p-lys1907ter (accessed [today's date]).

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