Is SETD2 p.Lys583fs (c.1748_1751del) pathogenic?

SETD2 p.Lys583fs (c.17481751del) is classified Pathogenic in SETD2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-05-13). No gnomAD frequency available for this variant; Associated with Luscan-Lumish syndrome.

What condition is associated with SETD2 p.Lys583fs (c.1748_1751del)?

SETD2 p.Lys583fs (c.1748_1751del) is associated with Luscan-Lumish syndrome (ClinVar).

How common is SETD2 p.Lys583fs (c.1748_1751del) in the general population?

SETD2 p.Lys583fs (c.1748_1751del) is no gnomAD frequency available for this variant (gnomAD).

SETD2 p.Lys583fs

c.1748_1751del · rs2043159037 · VCV1164031

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Luscan-Lumish syndrome

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 haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.67	GERP -1.3, phastCons 0.01

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: SETD2
Protein: p.Lys583fs
Coding: c.1748_1751del
MANE Select: NM_014159
dbSNP: rs2043159037
Type: Deletion
Location: chr3:47122885 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 583: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation)

Full SETD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Luscan-Lumish syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 c.5015+39_5015+40del Benign ★★ same condition
SETD2 c.6110-27_6110-26del Benign/Likely benign ★★ same condition
SETD2 p.Gly1726fs Pathogenic ★ same condition
SETD2 p.Lys1486fs Pathogenic ★ same condition
SETD2 p.Ser2238fs Pathogenic ★ same condition
SETD2 p.Gln2334_Ile2336del Uncertain significance ★ same condition
SETD2 p.Ser1268del Uncertain significance ★ same condition
SETD2 p.Ser2271del Uncertain significance ★ 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/setd2-p-lys583fs (accessed [today's date]).

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