Is SETD2 p.Arg136Ser (c.408G>T) pathogenic?

SETD2 p.Arg136Ser (c.408G>T) is classified Uncertain significance in SETD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-01). AlphaMissense: likely pathogenic (0.6402); No allele count reported in gnomAD v4.1 (AN 1,551,738); Associated with teratoma.

What condition is associated with SETD2 p.Arg136Ser (c.408G>T)?

SETD2 p.Arg136Ser (c.408G>T) is associated with teratoma (ClinVar).

How common is SETD2 p.Arg136Ser (c.408G>T) in the general population?

SETD2 p.Arg136Ser (c.408G>T) is no allele count reported in gnomAD v4.1 (AN 1,551,738) (gnomAD).

What do computational predictors say about SETD2 p.Arg136Ser (c.408G>T)?

AlphaMissense predicts likely pathogenic (score 0.6402) — an in-silico prediction, not a clinical call.

SETD2 p.Arg136Ser

c.408G>T · rs2106723146 · VCV2498266

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6402 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,738)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

teratoma

Computational evidence

Protein change
AlphaMissense	0.6402	likely pathogenic
REVEL	0.308	indeterminate
SaProt	LLR -4.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.51, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 40 kb · p 0.036 · regional, not allelic
Overall
CADD	19.65	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 1,551,738). 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.Arg136Ser
Coding: c.408G>T
MANE Select: NM_014159
dbSNP: rs2106723146
Type: single nucleotide variant
Location: chr3:47124228 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 136: a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation)

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

Disease context

teratoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 p.Arg136Thr 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
SETD2 p.Ala1121Thr 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-arg136ser (accessed [today's date]).

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