Is DST p.Lys4725Arg (c.14174A>G) pathogenic?

DST p.Lys4725Arg (c.14174A>G) is classified Benign in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 5.93%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Lys4725Arg (c.14174A>G)?

DST p.Lys4725Arg (c.14174A>G) is associated with hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

DST p.Lys4725Arg

Q: How common is DST p.Lys4725Arg (c.14174A>G) in the general population?

DST p.Lys4725Arg (c.14174A>G) is common (popmax 5.93%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.14174A>G · rs78484087 · VCV795663

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.93%, afr) — too common for a highly-penetrant pathogenic allele

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.
REVEL	0.029	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -1.9, phastCons 0.3
Regional constraint	o/e 0.90	unconstrained · MANE · 46 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	15.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.93% African / African-American · 4,448/75,028 alleles

Filtering AF 5.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.72%

Overall 0.335% 5,407/1,613,870 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.93%	17
Remaining individualsnot grpmax-eligible	0.469%	213
Admixed American	0.402%	249
Middle Eastern	0.148%	674
European (non-Finnish)	0.0341%	2,935
South Asian	0.0154%	6,505

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.Lys4725Arg
Coding: c.14174A>G
MANE Select: NM_001374736
dbSNP: rs78484087
Type: single nucleotide variant
Location: chr6:56561444 (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

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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-lys4725arg (accessed [today's date]).

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