Is SETD2 p.Lys57Arg (c.170A>G) pathogenic?

SETD2 p.Lys57Arg (c.170A>G) is classified Likely benign in SETD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-26). AlphaMissense: likely benign (0.1776); No allele count reported in gnomAD v4.1 (AN 1,551,810); Associated with autism spectrum disorder.

What condition is associated with SETD2 p.Lys57Arg (c.170A>G)?

SETD2 p.Lys57Arg (c.170A>G) is associated with autism spectrum disorder (ClinVar).

How common is SETD2 p.Lys57Arg (c.170A>G) in the general population?

SETD2 p.Lys57Arg (c.170A>G) is no allele count reported in gnomAD v4.1 (AN 1,551,810) (gnomAD).

What do computational predictors say about SETD2 p.Lys57Arg (c.170A>G)?

AlphaMissense predicts likely benign (score 0.1776) — an in-silico prediction, not a clinical call.

SETD2 p.Lys57Arg

c.170A>G · rs2106728625 · VCV2429922

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1776 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,810)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autism spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.1776	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 40 kb · p 0.036 · regional, not allelic
Overall
CADD	23.2	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 1,551,810). 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.Lys57Arg
Coding: c.170A>G
MANE Select: NM_014159
dbSNP: rs2106728625
Type: single nucleotide variant
Location: chr3:47124466 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB

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

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD2 p.Arg1708Ter Likely pathogenic ★ same condition
SETD2 p.Asn1488Lys Likely benign ★ ⚠ same condition
SETD2 p.Asp2004Gly Likely benign ★ same condition
SETD2 p.Gln2335Arg Likely benign ★ same condition
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

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-lys57arg (accessed [today's date]).

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