Is DSP p.Gly35= (c.105G>A) pathogenic?

DSP p.Gly35= (c.105G>A) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-06-01). Rare (popmax 0.958%, nfe); Associated with lethal acantholytic epidermolysis bullosa.

What condition is associated with DSP p.Gly35= (c.105G>A)?

DSP p.Gly35= (c.105G>A) is associated with lethal acantholytic epidermolysis bullosa, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Gly35= (c.105G>A) in the general population?

DSP p.Gly35= (c.105G>A) is rare (popmax 0.958%, nfe) (gnomAD).

How is Lethal acantholytic erosive disorder inherited?

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

DSP p.Gly35=

c.105G>A · rs77445784 · VCV36016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

rare (popmax 0.958%, nfe)

Conditions

lethal acantholytic epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4
Overall
CADD	9.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.958% European (non-Finnish) · 11,173/1,166,514 alleles

Filtering AF 0.943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.937%

Overall 0.785% 12,438/1,584,904 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.958%	104
Remaining individualsnot grpmax-eligible	0.753%	133
Admixed American	0.681%	147
Amishnot grpmax-eligible	0.658%	152
Middle Eastern	0.431%	232
Finnishnot grpmax-eligible	0.253%	395
African / African-American	0.176%	568
Ashkenazi Jewishnot grpmax-eligible	0.152%	660
South Asian	0.0713%	1,403

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.Gly35=
Coding: c.105G>A
MANE Select: NM_004415
dbSNP: rs77445784
Type: single nucleotide variant
Location: chr6:7542020 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 35: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region

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 keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis woolly hair-skin fragility syndrome

For Lethal acantholytic erosive disorder (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

DSP p.Gly35Ala Conflicting classifications of pathogenicity ★ same residue
DSP p.Gly35Arg Uncertain significance ★ same residue
DSP p.Gly35Val Uncertain significance ★ 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

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-gly35 (accessed [today's date]).

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