Is DST p.Arg6718His (c.20153G>A) pathogenic?

DST p.Arg6718His (c.20153G>A) is classified Conflicting classifications of pathogenicity in DST (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-17). Low-frequency (popmax 1.89%, eas); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Arg6718His (c.20153G>A) in the general population?

DST p.Arg6718His (c.20153G>A) is low-frequency (popmax 1.89%, eas) (gnomAD).

DST p.Arg6718His

Q: What condition is associated with DST p.Arg6718His (c.20153G>A)?

DST p.Arg6718His (c.20153G>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 is Epidermolysis bullosa simplex due to BP230 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.20153G>A · rs79728438 · VCV1166338

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.89%, eas)

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	0.271	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 46 kb · p 3.7e-11 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.89% East Asian · 846/44,854 alleles

Filtering AF 1.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.74%

Overall 0.0816% 1,317/1,613,134 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.89%	53
Ashkenazi Jewishnot grpmax-eligible	0.199%	501
African / African-American	0.155%	646
Remaining individualsnot grpmax-eligible	0.0593%	1,687
Admixed American	0.0217%	4,608
European (non-Finnish)	0.0202%	4,956
Middle Eastern	0.0165%	6,050
South Asian	0.00549%	18,208
Finnishnot grpmax-eligible	0.00313%	31,997

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.Arg6718His
Coding: c.20153G>A
MANE Select: NM_001374736
dbSNP: rs79728438
Type: single nucleotide variant
Location: chr6:56497449 (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

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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
DST p.Gln1366Ter 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-arg6718his (accessed [today's date]).

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