Is DST p.Ala1677Ser (c.5029G>T) pathogenic?

DST p.Ala1677Ser (c.5029G>T) is classified Uncertain significance in DST (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-09). Ultra-rare (popmax 0.0234%, nfe); Associated with Inborn genetic diseases.

How common is DST p.Ala1677Ser (c.5029G>T) in the general population?

DST p.Ala1677Ser (c.5029G>T) is ultra-rare (popmax 0.0234%, nfe) (gnomAD).

DST p.Ala1677Ser

Q: What condition is associated with DST p.Ala1677Ser (c.5029G>T)?

DST p.Ala1677Ser (c.5029G>T) is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

c.5029G>T · rs370590691 · VCV646788

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.105	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 36 kb · p 0.7 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0234% European (non-Finnish) · 276/1,177,140 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0203%

Overall 0.0177% 284/1,607,822 alleles · ultra-rare exomes 272/1,455,716 · genomes 12/152,106 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0234%	4,265
Remaining individualsnot grpmax-eligible	0.00642%	15,566
Admixed American	0.00169%	59,200
Finnishnot grpmax-eligible	0.00157%	63,864
African / African-American	0.00134%	74,666
South Asian	0.00111%	89,706

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.Ala1677Ser
Coding: c.5029G>T
MANE Select: NM_001374736
dbSNP: rs370590691
Type: single nucleotide variant
Location: chr6:56614385 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary sensory and autonomic neuropathy type 6 epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Similar variants

DST p.Ala1677Pro 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-ala1677ser (accessed [today's date]).

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