Is SETD2 p.Lys772Glu (c.2314A>G) pathogenic?

SETD2 p.Lys772Glu (c.2314A>G) is classified Benign/Likely benign in SETD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-28). AlphaMissense: likely benign (0.0931); Ultra-rare (popmax 0.0586%, afr); Associated with Inborn genetic diseases.

What condition is associated with SETD2 p.Lys772Glu (c.2314A>G)?

SETD2 p.Lys772Glu (c.2314A>G) is associated with Inborn genetic diseases, Luscan-Lumish syndrome (ClinVar).

How common is SETD2 p.Lys772Glu (c.2314A>G) in the general population?

SETD2 p.Lys772Glu (c.2314A>G) is ultra-rare (popmax 0.0586%, afr) (gnomAD).

What do computational predictors say about SETD2 p.Lys772Glu (c.2314A>G)?

AlphaMissense predicts likely benign (score 0.0931) — an in-silico prediction, not a clinical call.

SETD2 p.Lys772Glu

c.2314A>G · rs142099709 · VCV732362

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0586%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0931	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -6.13	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,229 bp · p 0.25 · regional, not allelic
Overall
CADD	21.8	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 0.0586% African / African-American · 44/75,076 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.00409% 66/1,614,226 alleles · ultra-rare exomes 44/1,461,836 · genomes 22/152,390 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0586%	1,706
Admixed American	0.0167%	6,002
Remaining individualsnot grpmax-eligible	0.0128%	7,814
European (non-Finnish)	0.000339%	295,008

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.Lys772Glu
Coding: c.2314A>G
MANE Select: NM_014159
dbSNP: rs142099709
Type: single nucleotide variant
Location: chr3:47122322 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.81 · 43 PDB
Residue 772: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Luscan-Lumish syndrome

Similar variants

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
SETD2 p.Arg1197Thr 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-lys772glu (accessed [today's date]).

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