Is DST p.Val1354= (c.4062C>T) pathogenic?

DST p.Val1354= (c.4062C>T) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 4.27%, afr); Associated with epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency.

How common is DST p.Val1354= (c.4062C>T) in the general population?

DST p.Val1354= (c.4062C>T) is low-frequency (popmax 4.27%, afr) (gnomAD).

DST p.Val1354=

Q: What condition is associated with DST p.Val1354= (c.4062C>T)?

DST p.Val1354= (c.4062C>T) 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.4062C>T · rs78600049 · VCV357600

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.27%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -5.1
Overall
CADD	0.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.27% African / African-American · 3,204/74,978 alleles

Filtering AF 4.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.1%

Overall 0.233% 3,765/1,613,884 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.27%	23
Admixed American	0.412%	243
Remaining individualsnot grpmax-eligible	0.325%	308
Middle Eastern	0.148%	674
South Asian	0.0121%	8,278
European (non-Finnish)	0.00771%	12,966

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.Val1354=
Coding: c.4062C>T
MANE Select: NM_001374736
dbSNP: rs78600049
Type: single nucleotide variant
Location: chr6:56631291 (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.Gln1354Lys Conflicting classifications of pathogenicity ★ 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-val1354 (accessed [today's date]).

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