Is SET p.Asp264del (c.786TGA[2]) pathogenic?

SET p.Asp264del (c.786TGA[2]) is classified Likely benign in SET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). Ultra-rare (popmax 0.037%, afr); Associated with Inborn genetic diseases.

What condition is associated with SET p.Asp264del (c.786TGA[2])?

SET p.Asp264del (c.786TGA[2]) is associated with Inborn genetic diseases (ClinVar).

How common is SET p.Asp264del (c.786TGA[2]) in the general population?

SET p.Asp264del (c.786TGA[2]) is ultra-rare (popmax 0.037%, afr) (gnomAD).

SET p.Asp264del

c.786TGA[2] · rs573205355 · VCV2208661

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.037%, afr)

Conditions

Inborn genetic diseases

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 1.3	GERP 0.015, phastCons 1
Overall
CADD	19.42	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 0.037% African / African-American · 27/72,946 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.018% 277/1,538,646 alleles · ultra-rare exomes 251/1,386,752 · genomes 26/151,894 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.037%	2,702
European (non-Finnish)	0.0195%	5,122
Remaining individualsnot grpmax-eligible	0.0184%	5,429
Middle Eastern	0.0168%	5,966
South Asian	0.0152%	6,592
Admixed American	0.00573%	17,447
East Asian	0.00462%	21,644

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.Asp264del
Coding: c.786TGA[2]
MANE Select: NM_003011
dbSNP: rs573205355
Type: Microsatellite
Location: chr9:128694016 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 264: a UniProt-annotated variant site (in mrd58); the 'disordered' region

Full SET 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

SET p.Asp260Glu Uncertain significance ★★ ⚠ same condition
SET p.Glu261Asp Uncertain significance ★★ ⚠ same condition
SET p.Asp235Glu Likely benign ★★ same condition
SET p.Gly200fs Pathogenic ★ same condition
SET p.Pro151fs Pathogenic ★ same condition
SET c.492+4T>C Uncertain significance ★ same condition
SET p.Glu233Gly Uncertain significance ★ ⚠ same condition
SET p.Glu271Asp Uncertain significance ★ ⚠ 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/set-p-asp264del (accessed [today's date]).

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