Is SETD2 p.Tyr428del (c.1279TAT[1]) pathogenic?

SETD2 p.Tyr428del (c.1279TAT[1]) is classified Uncertain significance in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). Very rare (popmax 6.44e-05%); Associated with Inborn genetic diseases.

What condition is associated with SETD2 p.Tyr428del (c.1279TAT[1])?

SETD2 p.Tyr428del (c.1279TAT[1]) is associated with Inborn genetic diseases (ClinVar).

How common is SETD2 p.Tyr428del (c.1279TAT[1]) in the general population?

SETD2 p.Tyr428del (c.1279TAT[1]) is very rare (popmax 6.44e-05%) (gnomAD).

SETD2 p.Tyr428del

c.1279TAT[1] · VCV3952840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.44e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.44e-05%

Overall 6.44e-05% 1/1,551,658 alleles · very rare exomes 1/1,399,372 · genomes 0/152,286 · joint denominator

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: SETD2
Protein: p.Tyr428del
Coding: c.1279TAT[1]
MANE Select: NM_014159
Type: Microsatellite
Location: chr3:47123352 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 428: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 c.4457_4460delAGAA Pathogenic ★★ same condition
SETD2 p.Asp429_Ser430insTer Pathogenic/Likely pathogenic ★★ same condition
SETD2 p.Glu610fs Pathogenic ★ same condition
SETD2 p.Pro194_Pro196del Uncertain significance ★ same condition
SETD2 c.4715+5G>A Uncertain significance ★★ same condition
SETD2 p.Arg1197Thr Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg368Gln Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg540Gln 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-tyr428del (accessed [today's date]).

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