Is DST p.Tyr8fs (c.22del) pathogenic?

DST p.Tyr8fs (c.22del) is classified Conflicting classifications of pathogenicity in DST (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-04-28). Ultra-rare (popmax 0.0649%, nfe); Associated with DST-related disorder.

How common is DST p.Tyr8fs (c.22del) in the general population?

DST p.Tyr8fs (c.22del) is ultra-rare (popmax 0.0649%, nfe) (gnomAD).

DST p.Tyr8fs

Q: What condition is associated with DST p.Tyr8fs (c.22del)?

DST p.Tyr8fs (c.22del) is associated with DST-related disorder, hereditary sensory and autonomic neuropathy type 6, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

c.22del · rs775912185 · VCV282605

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0649%, nfe)

Conditions

DST-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Overall
CADD	18.34	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0649% European (non-Finnish) · 766/1,179,964 alleles

Filtering AF 0.0611% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.0522% 843/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0649%	1,540
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.05%	2,001
African / African-American	0.0107%	9,382
Finnishnot grpmax-eligible	0.00313%	31,999

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.Tyr8fs
Coding: c.22del
MANE Select: NM_001374736 · reported on NM_001723
dbSNP: rs775912185
Type: Deletion
Location: chr6:56642767 (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

DST-related disorder

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

Similar variants

DST p.Tyr8Cys Uncertain significance ★★ same residue
DST p.Ala1128fs Pathogenic ★★ same condition
DST p.Ala7253fs Pathogenic ★★ same condition
DST p.Arg4211_Lys4215del Uncertain significance ★★ same condition
DST p.Ser2388fs Uncertain significance ★★ same condition
DST c.14441-7del Benign/Likely benign ★★ same condition
DST c.21676-15_21676-14del Benign/Likely benign ★★ same condition
DST c.2697+16del Benign/Likely benign ★★ 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-tyr8fs (accessed [today's date]).

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