DST p.Gln1748Pro

Q: Is DST p.Gln1748Pro (c.5243A>C) pathogenic?

DST p.Gln1748Pro (c.5243A>C) is classified Benign in DST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Common (popmax 7%, 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.Gln1748Pro (c.5243A>C)?

DST p.Gln1748Pro (c.5243A>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 common is DST p.Gln1748Pro (c.5243A>C) in the general population?

DST p.Gln1748Pro (c.5243A>C) is common (popmax 7%, 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.5243A>C · rs61263396 · VCV1167590

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7%, 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.
REVEL	0.165	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 2.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic
Overall
CADD	19.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7% African / African-American · 5,177/73,930 alleles

Filtering AF 6.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.78%

Overall 0.379% 5,949/1,568,104 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7%	14
Admixed American	0.58%	172
Remaining individualsnot grpmax-eligible	0.551%	181
Middle Eastern	0.251%	398
South Asian	0.02%	4,994
European (non-Finnish)	0.00831%	12,029

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.Gln1748Pro
Coding: c.5243A>C
MANE Select: NM_001374736
dbSNP: rs61263396
Type: single nucleotide variant
Location: chr6:56610467 (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.Lys1748Arg Uncertain significance ★ same residue
DST p.Gln1748= Likely benign ★ 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

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-gln1748pro (accessed [today's date]).

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