Is SETD2 p.Gln2334Arg (c.7001A>G) pathogenic?

SETD2 p.Gln2334Arg (c.7001A>G) is classified Uncertain significance in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely pathogenic (0.5722); Very rare (popmax 0.00223%, eas).

How common is SETD2 p.Gln2334Arg (c.7001A>G) in the general population?

SETD2 p.Gln2334Arg (c.7001A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SETD2 p.Gln2334Arg (c.7001A>G)?

AlphaMissense predicts likely pathogenic (score 0.5722) — an in-silico prediction, not a clinical call.

SETD2 p.Gln2334Arg

c.7001A>G · rs2107549649 · VCV1695570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5722	likely pathogenic
REVEL	0.124	moderately benign-leaning
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.66, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 19 kb · p 0.00059 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.00223% East Asian · 1/44,856 alleles

Overall 6.2e-05% 1/1,613,342 alleles · very rare exomes 1/1,461,092 · genomes 0/152,250 · joint denominator

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: SETD2
Protein: p.Gln2334Arg
Coding: c.7001A>G
MANE Select: NM_014159
dbSNP: rs2107549649
Type: single nucleotide variant
Location: chr3:47046584 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 2334: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'low charge region' region

Full SETD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD2 p.Gln2334= Likely benign ★ same residue
SETD2 p.Gln2334_Ile2336del Uncertain significance ★ same residue
SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same type
SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same type
SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same type
SETD2 p.Arg441Ter Likely pathogenic ★★ same type
SETD2 p.Glu1718Lys Likely pathogenic ★★ ⚠ same type
SETD2 c.4715+5G>A Uncertain significance ★★ 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/setd2-p-gln2334arg (accessed [today's date]).

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