Is DST p.Ala1017= (c.3051G>A) pathogenic?

DST p.Ala1017= (c.3051G>A) is classified Likely benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-22). Rare (popmax 0.155%, afr); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Ala1017= (c.3051G>A) in the general population?

DST p.Ala1017= (c.3051G>A) is rare (popmax 0.155%, afr) (gnomAD).

DST p.Ala1017=

Q: What condition is associated with DST p.Ala1017= (c.3051G>A)?

DST p.Ala1017= (c.3051G>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.3051G>A · rs143352267 · VCV703452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.155%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -5.2
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.155% African / African-American · 116/75,006 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00868% 140/1,612,630 alleles · rare exomes 81/1,460,402 · genomes 59/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.155%	647
Admixed American	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.008%	12,496
East Asian	0.00223%	44,862
South Asian	0.0022%	45,536
European (non-Finnish)	0.000509%	196,611

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.Ala1017=
Coding: c.3051G>A
MANE Select: NM_001374736
dbSNP: rs143352267
Type: single nucleotide variant
Location: chr6:56636566 (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.Ala1017Val 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-ala1017 (accessed [today's date]).

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