Is DST p.Leu1636= (c.4906T>C) pathogenic?

DST p.Leu1636= (c.4906T>C) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-26). Rare (popmax 0.579%, afr); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Leu1636= (c.4906T>C) in the general population?

DST p.Leu1636= (c.4906T>C) is rare (popmax 0.579%, afr) (gnomAD).

DST p.Leu1636=

Q: What condition is associated with DST p.Leu1636= (c.4906T>C)?

DST p.Leu1636= (c.4906T>C) 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.4906T>C · rs147406105 · VCV357590

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.579%, afr)

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 0.036	GERP -5.8
Overall
CADD	2.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.579% African / African-American · 434/74,982 alleles

Filtering AF 0.534% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.516%

Overall 0.0287% 463/1,612,924 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.579%	173
Middle Eastern	0.033%	3,029
Remaining individualsnot grpmax-eligible	0.0256%	3,904
Admixed American	0.0117%	8,571
South Asian	0.0011%	91,050
European (non-Finnish)	0.000254%	393,091

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.Leu1636=
Coding: c.4906T>C
MANE Select: NM_001374736
dbSNP: rs147406105
Type: single nucleotide variant
Location: chr6:56624553 (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.Thr1636Lys 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
DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Gln1124Ter Pathogenic/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/dst-p-leu1636 (accessed [today's date]).

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