Is SETD2 p.Arg401Leu (c.1202G>T) pathogenic?

SETD2 p.Arg401Leu (c.1202G>T) is classified Uncertain significance in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.5576); No allele count reported in gnomAD v4.1 (AN 1,551,566); Associated with Inborn genetic diseases.

What condition is associated with SETD2 p.Arg401Leu (c.1202G>T)?

SETD2 p.Arg401Leu (c.1202G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETD2 p.Arg401Leu (c.1202G>T) in the general population?

SETD2 p.Arg401Leu (c.1202G>T) is no allele count reported in gnomAD v4.1 (AN 1,551,566) (gnomAD).

What do computational predictors say about SETD2 p.Arg401Leu (c.1202G>T)?

AlphaMissense predicts ambiguous (score 0.5576) — an in-silico prediction, not a clinical call.

SETD2 p.Arg401Leu

c.1202G>T · rs374918549 · VCV2307257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5576 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,566)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5576	ambiguous
REVEL	0.14	moderately benign-leaning
SaProt	LLR -8.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP 0.57, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,229 bp · p 0.25 · regional, not allelic
Overall
CADD	21.3	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

No allele count reported in gnomAD v4.1 (AN 1,551,566). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETD2
Protein: p.Arg401Leu
Coding: c.1202G>T
MANE Select: NM_014159
dbSNP: rs374918549
Type: single nucleotide variant
Location: chr3:47123434 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 401: 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

Similar variants

SETD2 p.Arg401Gln Uncertain significance ★★ ⚠ same residue
SETD2 p.Arg401Trp Uncertain significance ★ ⚠ same residue
SETD2 c.4715+5G>A Uncertain significance ★★ same condition
SETD2 p.Arg1197Thr Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg368Gln Uncertain significance ★★ ⚠ same condition
SETD2 p.Arg540Gln Uncertain significance ★★ ⚠ same condition
SETD2 p.Asn1303Ser Uncertain significance ★★ ⚠ same condition
SETD2 p.Asn840Ser 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-arg401leu (accessed [today's date]).

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