Is SETD2 p.Asp2064fs (c.6190_6191dup) pathogenic?

SETD2 p.Asp2064fs (c.61906191dup) is classified Likely pathogenic in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). Associated with SETD2-related disorder.

What condition is associated with SETD2 p.Asp2064fs (c.6190_6191dup)?

SETD2 p.Asp2064fs (c.6190_6191dup) is associated with SETD2-related disorder (ClinVar).

SETD2 p.Asp2064fs

c.6190_6191dup · VCV4538287

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SETD2-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 haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.25	GERP -3.2, phastCons 0.94

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

Variant & gene context

Gene: SETD2
Protein: p.Asp2064fs
Coding: c.6190_6191dup
MANE Select: NM_014159
Type: Microsatellite
Location: chr3:47062264 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 2064: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'disordered' region

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

Disease context

SETD2-related disorder

Similar variants

SETD2 p.Asp2064Glu Uncertain significance ★ ⚠ same residue
SETD2 p.Glu1339del Uncertain significance same condition
SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same condition
SETD2 p.Glu1430Gly Uncertain significance ★★ ⚠ same condition
SETD2 p.Ser1056Leu Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg2040Ter Likely pathogenic ★ same condition
SETD2 p.Arg620Ter Likely pathogenic ★ same condition
SETD2 p.Asn1856fs 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/setd2-p-asp2064fs (accessed [today's date]).

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