Is SUMO2 p.Gln90His (c.270G>T) pathogenic?

SUMO2 p.Gln90His (c.270G>T) is classified Uncertain significance in SUMO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-31). AlphaMissense: likely pathogenic (0.9955); Absent from gnomAD v4.1.

How common is SUMO2 p.Gln90His (c.270G>T) in the general population?

SUMO2 p.Gln90His (c.270G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SUMO2 p.Gln90His (c.270G>T)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

SUMO2 p.Gln90His

c.270G>T · VCV3765740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -12.08	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 14 kb · p 7.6e-21 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SUMO2
Protein: p.Gln90His
Coding: c.270G>T
MANE Select: NM_006937
Type: single nucleotide variant
Location: chr17:75168357 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 26 PDB
Residue 90: the ubiquitin-like domain; a β-strand

Full SUMO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SUMO2 c.-28G>A 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/sumo2-p-gln90his (accessed [today's date]).

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