Is SETD2 p.Arg402Gln (c.1205G>A) pathogenic?

SETD2 p.Arg402Gln (c.1205G>A) is classified Benign/Likely benign in SETD2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-09-25). AlphaMissense: ambiguous (0.3473); Rare (popmax 0.112%, afr); Associated with Inborn genetic diseases.

What condition is associated with SETD2 p.Arg402Gln (c.1205G>A)?

SETD2 p.Arg402Gln (c.1205G>A) is associated with Inborn genetic diseases, Luscan-Lumish syndrome (ClinVar).

How common is SETD2 p.Arg402Gln (c.1205G>A) in the general population?

SETD2 p.Arg402Gln (c.1205G>A) is rare (popmax 0.112%, afr) (gnomAD).

What do computational predictors say about SETD2 p.Arg402Gln (c.1205G>A)?

AlphaMissense predicts ambiguous (score 0.3473) — an in-silico prediction, not a clinical call.

SETD2 p.Arg402Gln

c.1205G>A · rs182736967 · VCV767586

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3473 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3473	ambiguous
REVEL	0.147	moderately benign-leaning
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,229 bp · p 0.25 · regional, not allelic
Overall
CADD	26.3	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 0.112% African / African-American · 82/73,138 alleles

Filtering AF 0.0925% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0853%

Overall 0.00722% 112/1,551,542 alleles · rare exomes 60/1,399,300 · genomes 52/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	892
East Asian	0.0171%	5,846
Remaining individualsnot grpmax-eligible	0.00666%	15,026
Admixed American	0.00588%	16,993
European (non-Finnish)	0.00139%	71,685

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.Arg402Gln
Coding: c.1205G>A
MANE Select: NM_014159
dbSNP: rs182736967
Type: single nucleotide variant
Location: chr3:47123431 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 402: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region

Full SETD2 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

Also linked: Luscan-Lumish syndrome

Similar variants

SETD2 p.Arg402Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same condition
SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same condition
SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same condition
SETD2 c.4715+5G>A Uncertain significance ★★ same condition
SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same condition
SETD2 p.Ala679Val Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg1065Cys 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/setd2-p-arg402gln (accessed [today's date]).

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