Is DST p.Ala7639Val (c.22916C>T) pathogenic?

DST p.Ala7639Val (c.22916C>T) is classified Benign/Likely benign in DST (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Rare (popmax 0.214%, nfe); Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Ala7639Val (c.22916C>T)?

DST p.Ala7639Val (c.22916C>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.Ala7639Val (c.22916C>T) in the general population?

DST p.Ala7639Val (c.22916C>T) is rare (popmax 0.214%, nfe) (gnomAD).

DST p.Ala7639Val

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.22916C>T · rs201429821 · VCV796218

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.214%, 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	0.055	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP -1.8, phastCons 0.31
Regional constraint	o/e 1.01	unconstrained · MANE · 4,631 bp · p 0.86 · regional, not allelic
Overall
CADD	7.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% European (non-Finnish) · 2,518/1,176,458 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.209% 3,356/1,609,280 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.07%	93
European (non-Finnish)grpmax	0.214%	467
Remaining individualsnot grpmax-eligible	0.196%	510
African / African-American	0.016%	6,248
Admixed American	0.015%	6,654
East Asian	0.0134%	7,457
Ashkenazi Jewishnot grpmax-eligible	0.00679%	14,732
South Asian	0.00441%	22,682

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala7639Val
Coding: c.22916C>T
MANE Select: NM_001374736
dbSNP: rs201429821
Type: single nucleotide variant
Location: chr6:56463608 (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 p.Ala7639= Likely benign ★ same residue
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

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-ala7639val (accessed [today's date]).

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