Is DSP p.Arg907Ser (c.2719C>A) pathogenic?

DSP p.Arg907Ser (c.2719C>A) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely pathogenic (0.5686); Very rare (popmax 8.47e-05%, nfe); Associated with lethal acantholytic epidermolysis bullosa.

What condition is associated with DSP p.Arg907Ser (c.2719C>A)?

DSP p.Arg907Ser (c.2719C>A) is associated with lethal acantholytic epidermolysis bullosa, arrhythmogenic right ventricular dysplasia 8, woolly hair-skin fragility syndrome (ClinVar).

How common is DSP p.Arg907Ser (c.2719C>A) in the general population?

DSP p.Arg907Ser (c.2719C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Lethal acantholytic erosive disorder inherited?

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

What do computational predictors say about DSP p.Arg907Ser (c.2719C>A)?

AlphaMissense predicts likely pathogenic (score 0.5686) — an in-silico prediction, not a clinical call.

DSP p.Arg907Ser

c.2719C>A · rs749051278 · VCV909887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5686 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

lethal acantholytic epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.5686	likely pathogenic
REVEL	0.109	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.2e-05% 1/1,613,964 alleles · very rare exomes 0/1,461,834 · genomes 1/152,130 · 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.Arg907Ser
Coding: c.2719C>A
MANE Select: NM_004415
dbSNP: rs749051278
Type: single nucleotide variant
Location: chr6:7576382 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 907: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'globular 1' 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

Also linked: 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.Arg907Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Arg907His Conflicting classifications of pathogenicity ★ ⚠ 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
DSP c.2297+1G>A Likely pathogenic ★★ same condition
DSP c.2298-1G>C 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-arg907ser (accessed [today's date]).

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