Is DST p.Thr1397fs (c.4189del) pathogenic?

DST p.Thr1397fs (c.4189del) is classified Pathogenic in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-15). Absent from gnomAD; Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Thr1397fs (c.4189del) in the general population?

DST p.Thr1397fs (c.4189del) is absent from gnomAD (gnomAD).

DST p.Thr1397fs

Q: What condition is associated with DST p.Thr1397fs (c.4189del)?

DST p.Thr1397fs (c.4189del) 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.4189del · rs772099949 · VCV2008355

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5.1	GERP 0.65, phastCons 0.98

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DST
Protein: p.Thr1397fs
Coding: c.4189del
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs772099949
Type: Deletion
Location: chr6:56619845 (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.Thr1397= Likely benign ★★ same residue
DST p.Thr1397Met Uncertain significance ★ same residue
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

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-thr1397fs (accessed [today's date]).

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