Is DST p.Pro1910fs (c.5729del) pathogenic?

DST p.Pro1910fs (c.5729del) is classified Pathogenic in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). Very rare (popmax 0.000593%, nfe); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Pro1910fs (c.5729del) in the general population?

DST p.Pro1910fs (c.5729del) is very rare (popmax 0.000593%, nfe) (gnomAD).

DST p.Pro1910fs

Q: What condition is associated with DST p.Pro1910fs (c.5729del)?

DST p.Pro1910fs (c.5729del) is associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency, hereditary sensory and autonomic neuropathy type 6 (ClinVar).

Q: How is Epidermolysis bullosa simplex due to BP230 deficiency inherited?

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

c.5729del · rs2536674321 · VCV2062076

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.088	GERP -5.3, phastCons 0.062

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,996 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,044 alleles · very rare exomes 7/1,461,858 · genomes 0/152,186 · 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: DST
Protein: p.Pro1910fs
Coding: c.5729del
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs2536674321
Type: Deletion
Location: chr6:56618305 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)

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

Disease context

epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary sensory and autonomic neuropathy type 6

For Epidermolysis bullosa simplex due to BP230 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

DST p.Ala1128fs Pathogenic ★★ same condition
DST p.Ala7253fs Pathogenic ★★ same condition
DST p.Arg4211_Lys4215del Uncertain significance ★★ same condition
DST p.Ser2388fs Uncertain significance ★★ same condition
DST c.14441-7del Benign/Likely benign ★★ same condition
DST c.21676-15_21676-14del Benign/Likely benign ★★ same condition
DST c.2697+16del Benign/Likely benign ★★ same condition
DST c.4830+20_4830+21del Likely benign ★★ 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/dst-p-pro1910fs (accessed [today's date]).

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