Is SETD2 p.Val768fs (c.2303_2304del) pathogenic?

SETD2 p.Val768fs (c.23032304del) is classified Pathogenic/Likely pathogenic in SETD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). No gnomAD frequency available for this variant.

How common is SETD2 p.Val768fs (c.2303_2304del) in the general population?

SETD2 p.Val768fs (c.2303_2304del) is no gnomAD frequency available for this variant (gnomAD).

SETD2 p.Val768fs

c.2303_2304del · rs2106675579 · VCV1176018

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 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 6	GERP 0.22, phastCons 1

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.Val768fs
Coding: c.2303_2304del
MANE Select: NM_014159
dbSNP: rs2106675579
Type: Microsatellite
Location: chr3:47122332 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 768: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in)

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

Similar variants

SETD2 p.Val768Leu Benign/Likely benign ★★ same residue
SETD2 c.4457_4460delAGAA Pathogenic ★★ same type
SETD2 p.Asp429_Ser430insTer Pathogenic/Likely pathogenic ★★ same type
SETD2 c.4918-78AC[17] Benign/Likely benign ★★ same type
SETD2 p.Asn806_Ser807insTer Pathogenic ★ same type
SETD2 p.Asp1841fs Likely pathogenic ★ same type
SETD2 p.Asp2064fs Likely pathogenic ★ same type
SETD2 p.Asp350fs Pathogenic ★ 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/setd2-p-val768fs (accessed [today's date]).

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