Is SETD5 p.Pro752fs (c.2255_2270delinsTTTGGCTCACC) pathogenic?

SETD5 p.Pro752fs (c.22552270delinsTTTGGCTCACC) is classified Pathogenic in SETD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14).

SETD5 p.Pro752fs

c.2255_2270delinsTTTGGCTCACC · VCV3337176

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 16 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Variant & gene context

Gene: SETD5
Protein: p.Pro752fs
Coding: c.2255_2270delinsTTTGGCTCACC
MANE Select: NM_001080517
Type: Indel
Location: chr3:9448539 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 752: a UniProt-annotated variant site (in mrd23)

Full SETD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD5 p.Pro752Ala Uncertain significance ★ ⚠ same residue
SETD5 p.Pro752Ser Uncertain significance ★ ⚠ same residue
SETD5 p.Ala1049fs Likely pathogenic ★ same type
SETD5 p.Arg1028fs Likely pathogenic ★ same type
SETD5 p.Ile298fs Likely pathogenic ★ same type
SETD5 p.Lys781_Lys782delinsAsnTer Pathogenic ★ same type
SETD5 p.Ala135del Uncertain significance ★ same type
SETD5 p.Ala288Asn Uncertain significance ★ 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/setd5-p-pro752fs (accessed [today's date]).

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