Is DSE p.Lys846fs (c.2538_2541del) pathogenic?

DSE p.Lys846fs (c.25382541del) is classified Likely pathogenic in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). Absent from gnomAD.

How common is DSE p.Lys846fs (c.2538_2541del) in the general population?

DSE p.Lys846fs (c.2538_2541del) is absent from gnomAD (gnomAD).

DSE p.Lys846fs

c.2538_2541del · rs1784207138 · VCV1690440

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 2.1, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSE
Protein: p.Lys846fs
Coding: c.2538_2541del
MANE Select: NM_013352
dbSNP: rs1784207138
Type: Microsatellite
Location: chr6:116437002 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB

Full DSE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TSPYL1 p.Val242fs Pathogenic/Likely pathogenic ★★ same type
DSE p.851DE[1] Uncertain significance ★★ same type
DSE p.Leu558fs Uncertain significance ★ same type

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/dse-p-lys846fs (accessed [today's date]).

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