DST p.Lys1358=

Q: Is DST p.Lys1358= (c.4074G>A) pathogenic?

DST p.Lys1358= (c.4074G>A) is classified Benign in DST (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 43.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

Q: What condition is associated with DST p.Lys1358= (c.4074G>A)?

DST p.Lys1358= (c.4074G>A) is associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency, hereditary sensory and autonomic neuropathy type 6 (ClinVar).

Q: How common is DST p.Lys1358= (c.4074G>A) in the general population?

DST p.Lys1358= (c.4074G>A) is common (popmax 43.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.4074G>A · rs2230862 · VCV357579

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 43.4%, afr) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4
Overall
CADD	3.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.4% African / African-American · 32,480/74,878 alleles

Filtering AF 43% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.8%

Overall 39.5% 637,316/1,613,622 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	48.3%	2
Ashkenazi Jewishnot grpmax-eligible	48.1%	2
African / African-Americangrpmax	43.4%	2
European (non-Finnish)	41.1%	2
Admixed American	40.6%	2
Remaining individualsnot grpmax-eligible	40.3%	2
Middle Eastern	36.5%	3
Finnishnot grpmax-eligible	32.9%	3
South Asian	26%	4
East Asian	20.7%	5

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys1358=
Coding: c.4074G>A
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs2230862
Type: single nucleotide variant
Location: chr6:56619960 (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.Arg1358Ter Pathogenic ★ same residue
DST p.Arg1358Pro Uncertain significance ★ same residue
DST p.Lys1358Gln Uncertain significance ★ same residue
DST c.22959+1G>A Likely pathogenic ★★ same condition
DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg22Ter Likely pathogenic ★★ same condition
DST p.Arg7329Ter 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-lys1358 (accessed [today's date]).

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