Is DST p.Ser2340Phe (c.7019C>T) pathogenic?

DST p.Ser2340Phe (c.7019C>T) is classified Uncertain significance in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Ultra-rare (popmax 0.0174%, afr); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Ser2340Phe (c.7019C>T)?

DST p.Ser2340Phe (c.7019C>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.Ser2340Phe (c.7019C>T) in the general population?

DST p.Ser2340Phe (c.7019C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

DST p.Ser2340Phe

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.7019C>T · rs146858008 · VCV1462075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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	0.305	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,914 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000991% 16/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,763
East Asian	0.00668%	14,960

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.Ser2340Phe
Coding: c.7019C>T
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs146858008
Type: single nucleotide variant
Location: chr6:56616448 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Residue 2340: 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

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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-ser2340phe (accessed [today's date]).

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