Is JARID2 p.Gln537fs (c.1609_1627del) pathogenic?

JARID2 p.Gln537fs (c.16091627del) is classified Likely pathogenic in JARID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-14). Associated with developmental delay with variable intellectual disability and dysmorphic facies.

What condition is associated with JARID2 p.Gln537fs (c.1609_1627del)?

JARID2 p.Gln537fs (c.1609_1627del) is associated with developmental delay with variable intellectual disability and dysmorphic facies (ClinVar).

JARID2 p.Gln537fs

c.1609_1627del · VCV4855941

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

developmental delay with variable intellectual disability and dysmorphic facies

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.2	GERP 0.75, phastCons 1

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

Variant & gene context

Gene: JARID2
Protein: p.Gln537fs
Coding: c.1609_1627del
MANE Select: NM_004973
Type: Deletion
Location: chr6:15496830 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 62.74 · 17 PDB
Residue 537: the 'disordered' region

Full JARID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay with variable intellectual disability and dysmorphic facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

JARID2 p.Gln1003fs Pathogenic ★ same condition
JARID2 p.Asn1155Tyr Uncertain significance ★★ ⚠ same condition
JARID2 p.Asn171Asp Uncertain significance ★★ ⚠ same condition
JARID2 p.Glu186Gln Uncertain significance ★★ ⚠ same condition
JARID2 p.Ser528Leu Uncertain significance ★★ ⚠ same condition
JARID2 c.1945+1G>A Likely pathogenic ★ same condition
JARID2 c.2731+1G>C Likely pathogenic ★ same condition
JARID2 c.324-149_493+2097dup 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/jarid2-p-gln537fs (accessed [today's date]).

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