Is DST p.Thr4117= (c.12351T>G) pathogenic?

DST p.Thr4117= (c.12351T>G) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.34%, afr); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Thr4117= (c.12351T>G)?

DST p.Thr4117= (c.12351T>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.Thr4117= (c.12351T>G) in the general population?

DST p.Thr4117= (c.12351T>G) is low-frequency (popmax 4.34%, afr) (gnomAD).

DST p.Thr4117=

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.12351T>G · rs16888032 · VCV795667

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.34%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -4.8
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.34% African / African-American · 3,254/74,986 alleles

Filtering AF 4.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.16%

Overall 0.264% 4,264/1,613,722 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.34%	23
Middle Eastern	0.726%	138
Remaining individualsnot grpmax-eligible	0.354%	283
Admixed American	0.3%	333
Ashkenazi Jewishnot grpmax-eligible	0.267%	375
Finnishnot grpmax-eligible	0.0438%	2,284
European (non-Finnish)	0.0385%	2,599
South Asian	0.00439%	22,759

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.Thr4117=
Coding: c.12351T>G
MANE Select: NM_001374736
dbSNP: rs16888032
Type: single nucleotide variant
Location: chr6:56594038 (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.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-thr4117 (accessed [today's date]).

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