Is DST p.Pro4607His (c.13820C>A) pathogenic?

DST p.Pro4607His (c.13820C>A) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.33%, nfe); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Pro4607His (c.13820C>A)?

DST p.Pro4607His (c.13820C>A) 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.Pro4607His (c.13820C>A) in the general population?

DST p.Pro4607His (c.13820C>A) is low-frequency (popmax 1.33%, nfe) (gnomAD).

DST p.Pro4607His

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.13820C>A · rs138967674 · VCV795661

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, nfe)

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	0.248	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 46 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.33% European (non-Finnish) · 15,660/1,178,996 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 1.09% 17,549/1,611,722 alleles · low-frequency exomes 16,430/1,459,508 · genomes 1,119/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.33%	75
Remaining individualsnot grpmax-eligible	1%	100
Ashkenazi Jewishnot grpmax-eligible	0.697%	144
South Asian	0.424%	236
Finnishnot grpmax-eligible	0.422%	237
Admixed American	0.405%	247
Middle Eastern	0.248%	403
African / African-American	0.193%	517
East Asian	0.00224%	44,666

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.Pro4607His
Coding: c.13820C>A
MANE Select: NM_001374736
dbSNP: rs138967674
Type: single nucleotide variant
Location: chr6:56569914 (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

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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-pro4607his (accessed [today's date]).

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