Is DST p.Arg5392Ter (c.16174C>T) pathogenic?

DST p.Arg5392Ter (c.16174C>T) is classified Pathogenic in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-14). Very rare (popmax 0.00017%, nfe); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Arg5392Ter (c.16174C>T)?

DST p.Arg5392Ter (c.16174C>T) is associated with hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

How common is DST p.Arg5392Ter (c.16174C>T) in the general population?

DST p.Arg5392Ter (c.16174C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

DST p.Arg5392Ter

Q: How is Hereditary sensory and autonomic neuropathy type 6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.16174C>T · rs755738894 · VCV1456005

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

hereditary sensory and autonomic neuropathy type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 61 of 104
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.39	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 1.1, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,860 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,552 alleles · very rare

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.Arg5392Ter
Coding: c.16174C>T
MANE Select: NM_001374736
dbSNP: rs755738894
Type: single nucleotide variant
Location: chr6:56552618 (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

hereditary sensory and autonomic neuropathy type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

For Hereditary sensory and autonomic neuropathy type 6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DST p.Arg5392Gln Uncertain significance ★★ same residue
DST p.Arg5392Gly 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

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-arg5392ter (accessed [today's date]).

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