Is SETDB1 p.Gln413Arg (c.1238A>G) pathogenic?

SETDB1 p.Gln413Arg (c.1238A>G) is classified Uncertain significance in SETDB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely benign (0.2591); Absent from gnomAD v4.1.

How common is SETDB1 p.Gln413Arg (c.1238A>G) in the general population?

SETDB1 p.Gln413Arg (c.1238A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETDB1 p.Gln413Arg (c.1238A>G)?

AlphaMissense predicts likely benign (score 0.2591) — an in-silico prediction, not a clinical call.

SETDB1 p.Gln413Arg

c.1238A>G · rs2527917240 · VCV2284237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2591	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 6,571 bp · p 1.1e-17 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: SETDB1
Protein: p.Gln413Arg
Coding: c.1238A>G
MANE Select: NM_001366418
dbSNP: rs2527917240
Type: single nucleotide variant
Location: chr1:150946983 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.45 · 26 PDB
Residue 413: the 'disordered' region

Full SETDB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETDB1 c.261-3T>C Likely benign ★★ same type
SETDB1 p.Ala1022Val Benign ★★ same type
SETDB1 p.Pro469= Benign ★★ same type
SETDB1 p.Pro530Leu Benign/Likely benign ★★ same type
SETDB1 p.Pro978Leu Likely benign ★★ same type
SETDB1 c.674-2A>G Uncertain significance ★ same type
SETDB1 p.Arg1244Leu Uncertain significance ★ ⚠ same type
SETDB1 p.Arg611Gln 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/setdb1-p-gln413arg (accessed [today's date]).

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