Is DST p.Asp4212= (c.12636C>T) pathogenic?

DST p.Asp4212= (c.12636C>T) is classified Benign in DST (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-19). Low-frequency (popmax 2.63%, eas); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Asp4212= (c.12636C>T)?

DST p.Asp4212= (c.12636C>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.Asp4212= (c.12636C>T) in the general population?

DST p.Asp4212= (c.12636C>T) is low-frequency (popmax 2.63%, eas) (gnomAD).

DST p.Asp4212=

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.12636C>T · rs74609186 · VCV795839

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.63%, 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.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.9	GERP -4.8
Overall
CADD	0.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.63% East Asian · 1,182/44,868 alleles

Filtering AF 2.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.46%

Overall 0.0838% 1,352/1,613,808 alleles · low-frequency exomes 1,235/1,461,632 · genomes 117/152,176 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.63%	38
Remaining individualsnot grpmax-eligible	0.138%	726
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,466
Middle Eastern	0.0165%	6,062
South Asian	0.0143%	7,006
Admixed American	0.00667%	14,997
African / African-American	0.00533%	18,749
European (non-Finnish)	0.00424%	23,597

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.Asp4212=
Coding: c.12636C>T
MANE Select: NM_001374736
dbSNP: rs74609186
Type: single nucleotide variant
Location: chr6:56593753 (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-asp4212 (accessed [today's date]).

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