Is DST p.Lys6449Ter (c.19345A>T) pathogenic?

DST p.Lys6449Ter (c.19345A>T) is classified Pathogenic/Likely pathogenic in DST (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-10-15). Absent from gnomAD v4.1; Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Lys6449Ter (c.19345A>T)?

DST p.Lys6449Ter (c.19345A>T) is associated with hereditary sensory and autonomic neuropathy type 6 (ClinVar).

How common is DST p.Lys6449Ter (c.19345A>T) in the general population?

DST p.Lys6449Ter (c.19345A>T) is absent from gnomAD v4.1 (gnomAD).

DST p.Lys6449Ter

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.19345A>T · rs1562435373 · VCV559659

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 76 of 104
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Overall
CADD	52.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DST
Protein: p.Lys6449Ter
Coding: c.19345A>T
MANE Select: NM_001374736
dbSNP: rs1562435373
Type: single nucleotide variant
Location: chr6:56506684 (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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DST p.Lys6449Arg 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-lys6449ter (accessed [today's date]).

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