Is DST p.Ile4015Phe (c.12043A>T) pathogenic?

DST p.Ile4015Phe (c.12043A>T) is classified Conflicting classifications of pathogenicity in DST (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.198%, mid); Associated with Inborn genetic diseases.

How common is DST p.Ile4015Phe (c.12043A>T) in the general population?

DST p.Ile4015Phe (c.12043A>T) is rare (popmax 0.198%, mid) (gnomAD).

DST p.Ile4015Phe

Q: What condition is associated with DST p.Ile4015Phe (c.12043A>T)?

DST p.Ile4015Phe (c.12043A>T) 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).

c.12043A>T · rs201249286 · VCV663031

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.243	benign-leaning
Splicing
SpliceAI	Δ0.26	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.48	GERP -0.9, phastCons 0.22
Regional constraint	o/e 0.90	unconstrained · MANE · 46 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	7.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% Middle Eastern · 12/6,062 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0921% 1,486/1,613,828 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.198%	505
Admixed American	0.113%	883
European (non-Finnish)	0.112%	893
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
Remaining individualsnot grpmax-eligible	0.064%	1,562
South Asian	0.0143%	7,005
African / African-American	0.0107%	9,380
Finnishnot grpmax-eligible	0.00156%	63,988

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.Ile4015Phe
Coding: c.12043A>T
MANE Select: NM_001374736
dbSNP: rs201249286
Type: single nucleotide variant
Location: chr6:56597892 (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 p.Ile4015Val 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-ile4015phe (accessed [today's date]).

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