Is SETD5 p.Arg513fs (c.1538del) pathogenic?

SETD5 p.Arg513fs (c.1538del) is classified Pathogenic in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). Associated with Inborn genetic diseases.

What condition is associated with SETD5 p.Arg513fs (c.1538del)?

SETD5 p.Arg513fs (c.1538del) is associated with Inborn genetic diseases (ClinVar).

SETD5 p.Arg513fs

c.1538del · VCV3440222

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Inborn genetic diseases

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 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 2, phastCons 1

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

Variant & gene context

Gene: SETD5
Protein: p.Arg513fs
Coding: c.1538del
MANE Select: NM_001080517
Type: Deletion
Location: chr3:9447063 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 513: the 'disordered' region; a UniProt-annotated variant site (in mrd23)

Full SETD5 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

SETD5 p.Arg513_Lys514insTer Pathogenic ★ same residue
SETD5 p.Gly1086fs Pathogenic ★ same condition
SETD5 p.Lys600_Leu601insTer Pathogenic ★ same condition
SETD5 p.Pro871fs Pathogenic ★ same condition
SETD5 p.Thr658fs Pathogenic ★ same condition
SETD5 p.Arg513Ser Uncertain significance ★ ⚠ same residue
SETD5 p.Pro1415fs Conflicting classifications of pathogenicity ★ ⚠ same condition
SETD5 c.2347-7A>G 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/setd5-p-arg513fs (accessed [today's date]).

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