DST p.Val5041Ile

Q: Is DST p.Val5041Ile (c.15121G>A) pathogenic?

DST p.Val5041Ile (c.15121G>A) is classified Benign in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 11.6%, 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.Val5041Ile (c.15121G>A)?

DST p.Val5041Ile (c.15121G>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 common is DST p.Val5041Ile (c.15121G>A) in the general population?

DST p.Val5041Ile (c.15121G>A) is common (popmax 11.6%, 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.15121G>A · rs62621210 · VCV1164484

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 11.6%, 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	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.78, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 46 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	15.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.6% African / African-American · 8,564/73,746 alleles

Filtering AF 11.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 4.43% 70,204/1,583,480 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.6%	9
European (non-Finnish)	4.66%	21
Ashkenazi Jewishnot grpmax-eligible	4.43%	23
Remaining individualsnot grpmax-eligible	4.24%	24
Admixed American	2.06%	48
South Asian	1.71%	58
Finnishnot grpmax-eligible	1.33%	75
Middle Eastern	1.07%	93
East Asian	0.0135%	7,424

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.Val5041Ile
Coding: c.15121G>A
MANE Select: NM_001374736
dbSNP: rs62621210
Type: single nucleotide variant
Location: chr6:56555360 (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-val5041ile (accessed [today's date]).

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