Is DST p.Ile2017fs (c.6048_6049dup) pathogenic?

DST p.Ile2017fs (c.60486049dup) is classified Conflicting classifications of pathogenicity in DST (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-08). Rare (popmax 0.149%, sas); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Ile2017fs (c.6048_6049dup) in the general population?

DST p.Ile2017fs (c.6048_6049dup) is rare (popmax 0.149%, sas) (gnomAD).

DST p.Ile2017fs

Q: What condition is associated with DST p.Ile2017fs (c.6048_6049dup)?

DST p.Ile2017fs (c.6048_6049dup) 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.6048_6049dup · rs772013916 · VCV474536

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.149%, sas)

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 6	GERP 1.9, phastCons 1
Overall
CADD	23.3	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

Grpmax group 0.149% South Asian · 136/91,032 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.0708% 1,141/1,612,024 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.149%	669
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.0806%	1,241
Remaining individualsnot grpmax-eligible	0.048%	2,082
Admixed American	0.015%	6,667
African / African-American	0.00934%	10,710
East Asian	0.00669%	14,954
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,586
Finnishnot grpmax-eligible	0.00156%	64,018

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.Ile2017fs
Coding: c.6048_6049dup
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs772013916
Type: Microsatellite
Location: chr6:56617985 (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.Phe3921del Uncertain significance ★★ same condition
DST c.21403-23TG[17] Likely benign ★★ same condition
DST c.21403-23TG[18] Benign/Likely benign ★★ same condition
DST c.21403-23TG[19] Benign/Likely benign ★★ same condition
DST c.21403-23TG[20] Likely benign ★★ same condition
DST c.21403-23TG[6] Benign/Likely benign ★★ same condition
DST c.21403-23TG[8] Likely benign ★★ same condition
DST p.Leu1732fs 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/dst-p-ile2017fs (accessed [today's date]).

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