Is DST c.4142+4T>C pathogenic?

DST c.4142+4T>C is classified Uncertain significance in DST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-17). Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

How common is DST c.4142+4T>C in the general population?

DST c.4142+4T>C is ultra-rare (popmax 0.0166%, mid) (gnomAD).

DST c.4142+4T>C

Q: What condition is associated with DST c.4142+4T>C?

DST c.4142+4T>C is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

rs202054385 · VCV1354656

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +4	donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.38	GERP -5.1
Non-coding constraint	Z 2.73	1 kb window · o/e 0.80 · regional · uncalibrated
Overall
CADD	7.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,042 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00263%

Overall 0.00326% 52/1,595,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,042
Remaining individualsnot grpmax-eligible	0.00485%	20,601
European (non-Finnish)	0.00386%	25,878
African / African-American	0.00268%	37,281
Admixed American	0.00167%	59,814

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
Coding: c.4142+4T>C
MANE Select: NM_001374736
dbSNP: rs202054385
Type: single nucleotide variant
Location: chr6:56631207 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary sensory and autonomic neuropathy type 6 epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Similar variants

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
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-c-4142-plus-4t-c (accessed [today's date]).

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