Is DST p.Arg2467His (c.7400G>A) pathogenic?

DST p.Arg2467His (c.7400G>A) is classified Conflicting classifications of pathogenicity in DST (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0282%, nfe); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Arg2467His (c.7400G>A) in the general population?

DST p.Arg2467His (c.7400G>A) is ultra-rare (popmax 0.0282%, nfe) (gnomAD).

DST p.Arg2467His

Q: What condition is associated with DST p.Arg2467His (c.7400G>A)?

DST p.Arg2467His (c.7400G>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.7400G>A · rs200851382 · VCV664254

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, nfe)

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	0.25	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0282% European (non-Finnish) · 333/1,180,018 alleles

Filtering AF 0.0257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.0231% 373/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0282%	3,544
Remaining individualsnot grpmax-eligible	0.0192%	5,207
South Asian	0.0121%	8,280
African / African-American	0.012%	8,326
Admixed American	0.01%	10,000
East Asian	0.00445%	22,451

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.Arg2467His
Coding: c.7400G>A
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs200851382
Type: single nucleotide variant
Location: chr6:56616067 (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.Arg2467Cys 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-arg2467his (accessed [today's date]).

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