Is DST p.Arg7373= (c.22119A>G) pathogenic?

DST p.Arg7373= (c.22119A>G) is classified Benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-24). Low-frequency (popmax 2.05%, sas); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Arg7373= (c.22119A>G)?

DST p.Arg7373= (c.22119A>G) 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.Arg7373= (c.22119A>G) in the general population?

DST p.Arg7373= (c.22119A>G) is low-frequency (popmax 2.05%, sas) (gnomAD).

DST p.Arg7373=

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.22119A>G · rs192453671 · VCV796227

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, sas)

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.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -4.8
Overall
CADD	0.744	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.05% South Asian · 1,870/91,078 alleles

Filtering AF 1.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.94%

Overall 0.125% 2,015/1,613,978 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.05%	49
Remaining individualsnot grpmax-eligible	0.106%	947
Middle Eastern	0.0825%	1,212
East Asian	0.00668%	14,963
European (non-Finnish)	0.00576%	17,351
African / African-American	0.00266%	37,525
Admixed American	0.00167%	60,018

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.Arg7373=
Coding: c.22119A>G
MANE Select: NM_001374736
dbSNP: rs192453671
Type: single nucleotide variant
Location: chr6:56472098 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Residue 7373: the 'disordered' region

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 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-p-arg7373 (accessed [today's date]).

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