Is SET p.Gln91= (c.273A>G) pathogenic?

SET p.Gln91= (c.273A>G) is classified Conflicting classifications of pathogenicity in SET (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-01). Very rare (popmax 0.000678%, nfe).

How common is SET p.Gln91= (c.273A>G) in the general population?

SET p.Gln91= (c.273A>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

SET p.Gln91=

c.273A>G · rs753964058 · VCV3239452

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.53	loss · gain 0.15 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,930 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,590 alleles · very rare

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.Gln91=
Coding: c.273A>G
MANE Select: NM_003011
dbSNP: rs753964058
Type: single nucleotide variant
Location: chr9:128691999 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 91: the 'earmuff domain' region

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

Similar variants

SET c.663+5G>C Pathogenic ★★ same type
SET p.His105Tyr Likely pathogenic ★★ same type
SET p.Asp224Asn Uncertain significance ★★ ⚠ same type
SET p.Asp260Glu Uncertain significance ★★ ⚠ same type
SET p.Glu261Asp Uncertain significance ★★ ⚠ same type
SET p.Phe189Cys Uncertain significance ★★ ⚠ same type
SET c.132-17C>T Benign ★★ same type
SET c.493-14C>T 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-gln91 (accessed [today's date]).

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