Is SETSIP p.Glu216= (c.648G>A) pathogenic?

SETSIP p.Glu216= (c.648G>A) is classified Pathogenic in SETSIP (ClinVar, Single submitter, 1 submitter). Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SETSIP p.Glu216= (c.648G>A)?

SETSIP p.Glu216= (c.648G>A) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

How common is SETSIP p.Glu216= (c.648G>A) in the general population?

SETSIP p.Glu216= (c.648G>A) is absent from gnomAD v4.1 (gnomAD).

SETSIP p.Glu216=

c.648G>A · rs2526281838 · VCV1707481

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, autosomal dominant 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.4	GERP -2.9
Overall
CADD	1.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SETSIP
Protein: p.Glu216=
Coding: c.648G>A
MANE Select: NM_001287737
dbSNP: rs2526281838
Type: single nucleotide variant
Location: chr1:92074764 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.97
Residue 216: the 'disordered' region

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

Disease context

intellectual disability, autosomal dominant 58 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/setsip-p-glu216 (accessed [today's date]).

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