Is DST p.Val6448= (c.19344C>A) pathogenic?

DST p.Val6448= (c.19344C>A) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-28). Rare (popmax 0.64%, afr); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Val6448= (c.19344C>A)?

DST p.Val6448= (c.19344C>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.Val6448= (c.19344C>A) in the general population?

DST p.Val6448= (c.19344C>A) is rare (popmax 0.64%, afr) (gnomAD).

DST p.Val6448=

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.19344C>A · rs201031760 · VCV795662

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.64%, 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 2.8	GERP -4.2, phastCons 1
Overall
CADD	5.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.64% African / African-American · 480/74,954 alleles

Filtering AF 0.593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.574%

Overall 0.0574% 926/1,613,440 alleles · rare exomes 606/1,461,278 · genomes 320/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.64%	156
Admixed American	0.108%	922
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Middle Eastern	0.0661%	1,514
European (non-Finnish)	0.0282%	3,543

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.Val6448=
Coding: c.19344C>A
MANE Select: NM_001374736
dbSNP: rs201031760
Type: single nucleotide variant
Location: chr6:56506685 (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-val6448 (accessed [today's date]).

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