Is SET p.Glu229del (c.683AAG[1]) pathogenic?

SET p.Glu229del (c.683AAG[1]) is classified Uncertain significance in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 0.00231%, nfe).

How common is SET p.Glu229del (c.683AAG[1]) in the general population?

SET p.Glu229del (c.683AAG[1]) is very rare (popmax 0.00231%, nfe) (gnomAD).

SET p.Glu229del

c.683AAG[1] · rs772066011 · VCV2659548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00231%, nfe)

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 -1.2	GERP -0.031, phastCons 0.002
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GA-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% European (non-Finnish) · 27/1,168,258 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00194% 31/1,596,724 alleles · very rare exomes 28/1,445,732 · genomes 3/150,992 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00231%	43,269
South Asian	0.00224%	44,593
Admixed American	0.0017%	58,752
Remaining individualsnot grpmax-eligible	0.00161%	61,928

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: SET
Protein: p.Glu229del
Coding: c.683AAG[1]
MANE Select: NM_003011
dbSNP: rs772066011
Type: Microsatellite
Location: chr9:128693914 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB

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

Similar variants

SET p.Asp264del Likely benign ★★ same type
SET p.Glu243fs Pathogenic ★ same type
SET p.Ser140fs Pathogenic ★ same type
SET p.Ser148fs Pathogenic ★ same type
SET c.811-6_811-3del Uncertain significance ★ same type
SET p.Asp211del Uncertain significance ★ same type
SET p.Asp36del Uncertain significance ★ same type
SET c.810+65TA[11] Benign ★ 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/set-p-glu229del (accessed [today's date]).

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