Is DST p.Arg22Ter (c.64C>T) pathogenic?

DST p.Arg22Ter (c.64C>T) is classified Likely pathogenic in DST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). Very rare (popmax 0.00668%, eas); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Arg22Ter (c.64C>T)?

DST p.Arg22Ter (c.64C>T) is associated with hereditary sensory and autonomic neuropathy type 6 (ClinVar).

How common is DST p.Arg22Ter (c.64C>T) in the general population?

DST p.Arg22Ter (c.64C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

DST p.Arg22Ter

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.64C>T · rs779625484 · VCV1705347

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.2, phastCons 1
Overall
CADD	15.65	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 0.00668% East Asian · 3/44,882 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000889% 13/1,461,764 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
Remaining individualsnot grpmax-eligible	0.0048%	20,836
South Asian	0.0022%	45,536
European (non-Finnish)	0.000424%	235,992

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.Arg22Ter
Coding: c.64C>T
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs779625484
Type: single nucleotide variant
Location: chr6:56642725 (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.Arg22Gln Uncertain significance ★ same residue
DST p.Arg22Pro 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.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-arg22ter (accessed [today's date]).

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