Is DST p.Ser2041= (c.6123T>C) pathogenic?

DST p.Ser2041= (c.6123T>C) is classified Likely benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-26). Ultra-rare (popmax 0.0312%, eas); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Ser2041= (c.6123T>C)?

DST p.Ser2041= (c.6123T>C) 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.Ser2041= (c.6123T>C) in the general population?

DST p.Ser2041= (c.6123T>C) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

DST p.Ser2041=

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.6123T>C · rs766230887 · VCV1082273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, 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.
REVEL	0.088	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.4
Overall
CADD	15.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,890 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000991% 16/1,613,910 alleles · ultra-rare exomes 15/1,461,786 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,084

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.Ser2041=
Coding: c.6123T>C
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs766230887
Type: single nucleotide variant
Location: chr6:56617344 (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

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-ser2041 (accessed [today's date]).

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