Is DST p.Ala5677Val (c.17030C>T) pathogenic?

DST p.Ala5677Val (c.17030C>T) is classified Benign in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Common (popmax 6.01%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy type 6.

What condition is associated with DST p.Ala5677Val (c.17030C>T)?

DST p.Ala5677Val (c.17030C>T) is associated with hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

DST p.Ala5677Val

Q: How common is DST p.Ala5677Val (c.17030C>T) in the general population?

DST p.Ala5677Val (c.17030C>T) is common (popmax 6.01%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.17030C>T · rs145976321 · VCV795678

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.01%, afr) — too common for a highly-penetrant pathogenic allele

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	0.12	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 35 kb · p 0.66 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.01% African / African-American · 4,509/75,004 alleles

Filtering AF 5.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.81%

Overall 0.327% 5,278/1,613,386 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.01%	17
Admixed American	0.58%	172
Remaining individualsnot grpmax-eligible	0.464%	215
Middle Eastern	0.413%	242
South Asian	0.0231%	4,332
European (non-Finnish)	0.00721%	13,878

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.Ala5677Val
Coding: c.17030C>T
MANE Select: NM_001374736
dbSNP: rs145976321
Type: single nucleotide variant
Location: chr6:56532422 (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.Ala5677Thr Uncertain significance ★ 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-ala5677val (accessed [today's date]).

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